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Wnt signaling in cancer: therapeutic targeting of Wnt signaling beyond β-catenin and the destruction complex

Youn-Sang Jung, Jae-Il Park

Experimental & Molecular Medicine · 2020 · Review · CC BY

doi:10.1038/s12276-020-0380-6

Abstract

Wnt/β-catenin signaling is implicated in many physiological processes, including development, tissue homeostasis, and tissue regeneration. In human cancers, Wnt/β-catenin signaling is highly activated, which has led to the development of various Wnt signaling inhibitors for cancer therapies. Nonetheless, the blockade of Wnt signaling causes side effects such as impairment of tissue homeostasis and regeneration. Recently, several studies have identified cancer-specific Wnt signaling regulators. In this review, we discuss the Wnt inhibitors currently being used in clinical trials and suggest how additional cancer-specific regulators could be utilized to treat Wnt signaling-associated cancer.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 17, 2026. Paragraph numbers are ours, so an answer can point at one.

Introduction

Wnt signaling orchestrates various biological processes, such as cell proliferation, differentiation, organogenesis, tissue regeneration, and tumorigenesis–. Classically, Wnt signaling is divided into β-catenin-dependent (canonical, Wnt/β-catenin pathway) and β-catenin-independent (noncanonical, Wnt/planar cell polarity [PCP] and calcium pathway) signaling,. Canonical Wnt signaling mainly regulates cell proliferation, and noncanonical Wnt signaling controls cell polarity and movement. However, this terminological distinction is unclear, and has been questions by studies proposing the involvement of both β-catenin-dependent and β-catenin-independent Wnt signaling in tumorigenesis. For instance, APC and β-catenin are not only involved in cell proliferation but have also been linked to cell-to-cell adhesion. In this review, we will discuss an ongoing effort to inhibit Wnt signaling and suggest potential approaches to target Wnt signaling for cancer therapies proposed from recent studies.

Wnt signaling and clinical trials in human cancers

β-Catenin is a crucial signaling transducer in Wnt signaling,. The β-catenin protein destruction complex composed of adenomatous polyposis coli (APC), casein kinase 1 (CK1), glycogen synthase kinase 3α/β (GSK-3α/β), and AXIN1 tightly controls β-catenin via phosphorylation-mediated proteolysis,–. In this section, we briefly describe how genetic alterations of Wnt signaling contribute to tumorigenesis and introduce recent clinical trials that have aimed to inhibit Wnt signaling for cancer treatment.

The β-catenin destruction complex

Colorectal cancer (CRC) is the representative of human cancer caused by Wnt signaling hyperactivation,. CRC displays a high mutation frequency in APC (~70%)–. In 1991, APC mutation was identified as the cause of hereditary colon cancer syndrome, also called familial adenomatous polyposis. APC forms the β-catenin destruction complex in association with CK1, AXIN1, and GSK-3 and interacts with β-catenin,,. This protein destruction complex downregulates β-catenin through phosphorylation and ubiquitin-mediated protein degradation,–. Genetic mutations causing the loss of function of the destruction complex or gain of function of β-catenin lead to nuclear translocation of β-catenin, resulting in T-cell factor (TCF)4/β-catenin-mediated transactivation of Wnt target genes,. The Vogelstein group established a multistep tumorigenesis model of CRC. APC mutation is an early event that initiates CRC adenoma. CRC progression also requires additional genetic alterations in KRAS, PI3K, TGF-β, SMAD4, and TP53. Moreover, epigenetic silencing of negative regulators of Wnt signaling was also frequently found in the absence of APC mutations,. APC is a multifunctional protein. In addition to its role in β-catenin degradation, APC binds to actin and actin-regulating proteins–, which controls the interaction between E-cadherin and α-/β-catenin and various physiological processes, including migration and chromosomal fidelity–. Importantly, recent studies revealed that APC mutation is insufficient to fully activate Wnt signaling. Furthermore, even if APC is mutated, mutant APC still negatively regulates β-catenin to some extent,, which will be discussed later.

AXIN1 is a multidomain scaffolding protein that forms the β-catenin destruction complex in association with APC, CK1, and GSK3,,. In human cancer, AXIN1 mutations are scattered throughout the whole coding sequence of the AXIN1 gene,, which results in disassembly of the β-catenin destruction complex. As a priming kinase, CK1 initially phosphorylates β-catenin (Ser45), which induces the sequential phosphorylation of β-catenin by GSK3. Subsequently, phosphorylated β-catenin is recognized and degraded by E3 ubiquitin ligase (β-TrCP),–. GSK3 is a serine/threonine kinase that phosphorylates three serine/threonine residues of β-catenin (Ser33, Ser37, and Thr41),. Since GSK3 does not bind to β-catenin directly, AXIN1 and APC facilitate the interaction of GSK3 with β-catenin,. Moreover, unphosphorylated AXIN1 shows a low binding affinity to β-catenin, which is increased by phosphorylation of AXIN1 via GSK3 kinase activity,. Low-density lipoprotein receptor-related protein 5/6 (LRP5/6) coreceptor is also phosphorylated by CK1 and GSK3, leading to the recruitment of AXIN1 to the membrane–.

WNT ligands and receptors

Under physiological conditions, Wnt signaling is activated by the binding of secreted WNT ligands to LRP5/6 coreceptors and frizzled (FZD) receptors, which induces the recruitment of the protein destruction complex to the LRP receptors and the subsequent phosphorylation of the Ser/Pro-rich motif of the LRP cytoplasmic domain via GSK3,,. This event activates dishevelled (DVL) and inhibits GSK3, resulting in the inhibition of the phosphorylation-mediated β-catenin protein degradation and the stabilization/accumulation of β-catenin. Then, β-catenin undergoes nuclear translocation and transactivates Wnt target genes. The secretion of WNT ligands mainly depends on acylation by Porcupine (PORCN),. PORCN is a membrane-bound O-acyltransferase that mediates the palmitoylation of WNT ligands to induce their secretion. In line with this observation, PORCN shows increased genetic alterations in various human cancers, including esophageal, ovarian, uterine, lung, and cervical cancers.

Mutations in CTNNB1/β-catenin

Unlike CRC, in which the APC gene is frequently mutated, the CTNNB1 gene encoding β-catenin is predominantly mutated in hepatocellular carcinoma, endometrial cancer, and pancreatic cancer–. The CTNNB1/β-catenin gene harbors 16 exons. β-Catenin is mainly composed of three domains (N-terminal [~150 aa], armadillo repeat [12 copies; 550 aa], and C-terminal [~100 aa]). The N-terminal domain contains the phosphorylation sites for GSK3 and CK1,,,, which induces β-TrcP-mediated β-catenin degradation. The C-terminal domain is involved in transactivation of Wnt target genes via TCF/LEF interactions,–. The armadillo repeat domain interacts with various proteins, including E-cadherin, APC, AXIN1, and PYGOs/Pygopus,. In human cancer, the phosphorylation sites (Ser/Thr) in the N-terminal domain of CTNNB1/β-catenin are mutational hotspots,,, demonstrating that escape from destruction complex-mediated β-catenin protein degradation is a key process for Wnt signaling-induced tumorigenesis.

Therapeutic targeting of Wnt/β-catenin signaling

To suppress WNT ligands or receptors for cancer treatment, PORCN inhibitors, WNT ligand antagonists, and FZD antagonists/monoclonal antibodies have been examined in clinical trials of various Wnt signaling-associated human cancers (Table 1 and Fig. 1).

(i) PORCN inhibitors

WNT974 (LGK974; NIH clinical trial numbers [clinicaltrials.gov]: NCT02278133, NCT01351103, and NCT02649530), ETC-1922159 (ETC-159; NCT02521844), RXC004 (NCT03447470), and CGX1321 (NCT02675946 and NCT03507998) are orally administered PORCN inhibitors that commonly bind to PORCN in the endoplasmic reticulum–. Therefore, PORCN inhibitors block the secretion of WNT ligands through inhibition of posttranslational acylation of WNT ligands. However, similar to other cancer therapies targeting the Wnt pathway, skeletal side effects such as impairment of bone mass and strength and increase in bone resorption were caused by PORCN inhibitor administration.

(ii) SFRP and SFRP peptides

SFRPs (secreted frizzled-related proteins) are soluble proteins. Given the structural homology of SFRPs with the WNT ligand-binding domain in the FZD receptors, SFRPs function as antagonists that bind to WNT ligands and prevent Wnt signaling activation–. Indeed, SFRPs or SFRP-derived peptides showed tumor suppressive activity in preclinical models,.

(iii) FZD antagonist/monoclonal antibody

Vantictumab (OMP-18R5; NIH clinical trial numbers [clinicaltrials.gov]; NCT02005315, NCT01973309, NCT01345201, and NCT01957007) is a monoclonal antibody directly binding to FZD receptors, which blocks the binding of WNT ligands to FZD 1, 2, 5, 7, and 8. Ipafricept (OMP-54F28; NIH clinical trial numbers: NCT02069145, NCT02050178, NCT02092363, and NCT01608867) is a recombinant fusion protein that binds to a human IgG1 Fc fragment of FZD8,. These reagents negatively regulate Wnt/β-catenin signaling through their direct binding to FZD, which thereby disrupts the function of LRPs/FZDs. Alternatively, a way of targeting and killing cancer cells that express high FZD receptors is also being examined. OTSA101 is a humanized monoclonal antibody against FZD10. OTSA101-DTPA-90Y (NIH clinical trial number [clinicaltrials.gov] NCT01469975) is labeled with a β-radiation delivering-yttrium Y90 for OSTA101. OTSA101-DTPA-90Y selectively killed cancer cells highly expressing FZD10. The side effects of vanctumab include tiredness, diarrhea, vomiting, constipation, and abdominal pain. Vantictumab and ipafricept might also cause bone metabolism disorders,.

(iv) Targeting of LRP degradation and FZD endocytosis

Salinomycin, rottlerin, and monensin induce the phosphorylation of LRP6, resulting in the degradation of LRP6–. In addition, niclosamide promotes FZD1 endocytosis, which downregulates WNT3A-stimulated β-catenin stabilization. However, these reagents do not specifically target cancer-specific molecules, leading to side effects, including itchiness, abdominal pain, vomiting, dizziness, skin rash, and unpleasant taste,.

Given that the β-catenin protein destruction complex plays a crucial role in negatively regulating Wnt signaling, the restoration of this protein destruction complex may effectively inhibit Wnt/β-signaling. Tankyrase interacts with and degrades AXIN via ubiquitin-mediated proteasomal degradation–. Tankyrase inhibitors have been developed,–. Indeed, Tankyrase inhibitors have been shown to negatively regulate Wnt signaling in APC-mutated cancer cells–.

(i) Tankyrase inhibitors

Tankyrase inhibitors downregulate β-catenin stabilization. In preclinical studies, Tankyrase inhibitors, including XAV939, JW-55, RK-287107, and G007-LK, stabilized AXIN by inhibiting the poly-ADP-ribosylating enzyme Tankyrase–. However, currently, no clinical trials are being conducted with Tankyrase inhibitors.

(ii) CK1 agonist

Pyrvinium is an FDA-approved anti-helminthic drug. Pyrvinium binds to CK1 family members in vitro and promotes CK1 kinase activity.

β-Catenin contributes to tumorigenesis via transactivation of Wnt target genes such as CCND1, CD44, AXIN2, and MYC–. Thus, approaches inhibiting either β-catenin transcriptional activity or β-catenin target genes have been developed as potential therapeutic candidates for Wnt signaling-associated cancers (Table 1).

(i) Inhibitors of β-catenin transcriptional activity

β-Catenin/CBP binds to WRE (Wnt-responsive element; 5′-CTTTGA/TA/T-3′) and activates target gene transcription,. PRI-724 (ICG-001; NIH clinical trial numbers: NCT01302405, NCT02413853, NCT01764477, and NCT01606579) inhibits the interaction between CBP and β-catenin and prevents transcription of Wnt target genes. Moreover, various inhibitors of TCF/LEF and β-catenin interactions have been identified and evaluated in preclinical settings.

To transactivate Wnt target genes, β-catenin forms a transcriptional complex with coactivators, including BCL9 and PYGO,, which is inhibited by carnosic acid, compound 22, and SAH-BLC9,. In addition, Pyrvinium downregulates Wnt transcriptional activity through the degradation of PYGO.

(ii) Inhibitor of Wnt target genes

SM08502 (NIH clinical trial number NCT03355066) is a small molecule that inhibits serine and arginine-rich splicing factor (SRSF) phosphorylation and disrupts spliceosome activity. Upon oral administration, SM08502 was shown to downregulate Wnt signaling-controlled gene expression.

(iii) Proteasomal degradation of β-catenin

MSAB (methyl 3-[(4-methylphenyl)sulfonyl]amino-benzoate) binds to β-catenin and facilitates the ubiquitination-mediated proteasomal degradation of β-catenin,.

However, since β-catenin controls various physiological processes, downregulation of the transcriptional activity β-catenin was shown to induce diarrhea, hypophosphatemia, reversible elevated bilirubin, nausea, fatigue, anorexia, and thrombocytopenia,.

The β-catenin paradox

Wnt signaling hyperactivation by mutations in β-catenin destruction complex components or β-catenin itself contributes to tumorigenesis. In addition to APC mutations, β-catenin can be further activated by additional layers of regulation,,–, which demonstrated the complexity of Wnt signaling deregulation in cancer. Accumulating evidence supports the notion that additional regulatory processes contribute to Wnt signaling hyperactivation in cancer, as demonstrated in the following examples. (a) Mutant APC is still able to downregulate β-catenin,. (b) Even in the presence of APC mutations, blockade of WNT ligands triggers apoptosis or growth inhibition,,. (c) β-Catenin fold induction is essential for the activation of β-catenin target genes–. (d) Increased AXIN1 by Tankyrase inhibitor suppresses cell proliferation of cancer cells where Wnt/β-catenin signaling is genetically hyperactive,,,,. (e) Mutations in RNF43 and ZNRF3 E3 ligases that degrade Wnt receptors contribute to tumor development,. (f) Ras/MAPK signaling is also required for Wnt signaling activation,. These reports suggest that additional layers further enhance Wnt signaling activation in cancer.

The lysosome and Wnt signaling

The lysosome contains 40 types of hydrolytic enzymes, including cathepsins, which become active under acidic conditions. Lysosomal hydrolytic enzymes mediate the degradation of phagocytosed material and proteolysis of cytosolic proteins through fusion with the multivesicular body (MVB). Luminal acidification of the lysosome is required for lysosomal protein degradation, which is mainly controlled by vacuolar H+ transporters in the lysosomal membrane.

Recently, this classical view of lysosomal functions has evolved into new perspectives highlighting the roles of lysosomes in transcriptional regulation and metabolic homeostasis. In human cancer, lysosomal dysfunction is involved in the generation of building blocks, cell proliferation, metastasis, angiogenesis, and tumor suppressor degradation,.

It has been reported that Wnt signaling is involved in the endocytosis-mediated formation of the LRP signalosome into the MVB,. GSK3 in the LRP signalosome is sequestered into the MVB, which leads to an increase in the level of cytosolic β-catenin and inhibition of Wnt signaling. However, decreased GSK3 kinase activity by MVB sequestration lasts approximately 1 h,. Moreover, it is unclear how sequestrated APC, GSK3, AXIN, and CK1 in MVB are processed. A recent study showed that clathrin-mediated endocytosis is required for Wnt signaling activation, which is inhibited by APC. These studies suggest that vesicular acidification and trafficking also play crucial roles in controlling Wnt/β-catenin signaling through modulation of the protein destruction complex. Next, we discuss how APC is deregulated for Wnt signaling hyperactivation in cancer cells.

Wnt signaling activation requires v-ATPase (vacuolar H+-ATPase; an electrogenic H+ transporter),,. Previous studies imply that in cancer cells, the upregulation of v-ATPase activity might trigger abnormal Wnt/β-catenin signaling and contribute to Wnt signaling-dependent tumorigenesis. Growing evidence has demonstrated the effect of v-ATPase on various oncogenic processes, including cellular signaling, survival, drug resistance, and metastasis,. Moreover, the v-ATPase subunits are highly expressed in colorectal, breast, prostate, liver, ovarian, and pancreatic cancer cells–. The v-ATPase complex is composed of the V1 domain (in the cytosol) and V0 domain (on the membrane),. The V1 domain shows reversible disassociation from the V0 domain under physiological conditions, including glucose concentration, starvation of amino acids, and infection of cells by influenza virus–. Recently, TMEM9 (transmembrane protein 9) was identified as an activator of v-ATPase and is highly expressed in cancer. TMEM9 amplifies Wnt signaling through the v-ATPase-mediated lysosomal protein degradation of APC. Given that TMEM9 is highly expressed in CRC cells and that Tmem9 knockout mice are also viable, molecular targeting of TMEM9 may selectively suppress Wnt signaling activity in cancer cells.

Novel therapeutic target: v-ATPase

Conventional approaches targeting Wnt/β-catenin have led to various side effects, as mentioned above. Therefore, cancer-specific Wnt signaling regulators such as v-ATPase may be attractive molecular targets for Wnt signaling blockade. Chloroquine (CQ) and hydroxychloroquine (HCQ), inhibitors of lysosomes and autophagy, are clinically used for the treatment of diseases such as malaria and rheumatoid arthritis. While the mechanism of action of CQ and HCQ is somewhat unclear, other v-ATPase inhibitors, such as bafilomycin (BAF) and concanamycin (CON), directly bind to and inhibit v-ATPase,. Compared with CQ and HCQ, BAF and CON showed marked inhibition of Wnt/β-catenin signaling in CRC. In addition, BAF and CON displayed an antiproliferative effect in CRC patient-driven xenograft and animal models without toxicity to normal cells and animals. In addition, BAF and CON also strongly inhibit Wnt signaling activity in CRC cells, regardless of APC mutations. Thus, further research may lead to the development of not only safer but also more potent anti-v-ATPase drugs as cancer-specific Wnt/β-catenin inhibitors (Fig. 2).

Conclusion

Genetic and epigenetic deregulation of Wnt/β-catenin signaling contributes to human cancer, which has led to the development of extensive approaches targeting Wnt/β-catenin signaling as cancer therapies. Nonetheless, the blockade of Wnt signaling impairs tissue homeostasis and regeneration, which needs to be resolved. Recent studies have identified several Wnt signaling regulators whose expression is specific to cancer cells. These cancer-specific regulatory processes of Wnt signaling may be druggable vulnerabilities of Wnt signaling-associated cancer.

References 147

  1. 1.

    Acebron SP, Karaulanov E, Berger BS, Huang YL, Niehrs C. Mitotic wnt signaling promotes protein stabilization and regulates cell size. Mol. Cell. 2014;54:663-674.

    Not in our library10.1016/j.molcel.2014.04.014

  2. 2.

    Atlasi Y, et al. Wnt signaling regulates the lineage differentiation potential of mouse embryonic stem cells through Tcf3 down-regulation. PLoS Genet. 2013;9:e1003424.

    Not in our library10.1371/journal.pgen.1003424

  3. 3.

    Clevers H, Loh KM, Nusse R. Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control. Science. 2014;346:1248012.

    Not in our library10.1126/science.1248012

  4. 4.

    Green JL, Inoue T, Sternberg PW. Opposing Wnt pathways orient cell polarity during organogenesis. Cell. 2008;134:646-656.

    Not in our library10.1016/j.cell.2008.06.026

  5. 5.

    Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene. 2017;36:1461-1473.

    Not in our library10.1038/onc.2016.304

  6. 6.

    Grumolato L, et al. Canonical and noncanonical Wnts use a common mechanism to activate completely unrelated coreceptors. Genes Dev. 2010;24:2517-2530.

    Not in our library10.1101/gad.1957710

  7. 7.

    Katoh M. Canonical and non-canonical WNT signaling in cancer stem cells and their niches: Cellular heterogeneity, omics reprogramming, targeted therapy and tumor plasticity (Review). Int J. Oncol. 2017;51:1357-1369.

    Not in our library10.3892/ijo.2017.4129

  8. 8.

    Mirabelli Christopher K., Nusse Roel, Tuveson David A., Williams Bart O. Perspectives on the role of Wnt biology in cancer. Science Signaling. 2019;12(589):eaay4494.

    Not in our library10.1126/scisignal.aay4494

  9. 9.

    Amin N, Vincan E. The Wnt signaling pathways and cell adhesion. Front Biosci. (Landmark Ed.). 2012;17:784-804.

    Not in our library10.2741/3957

  10. 10.

    Li VS, et al. Wnt signaling through inhibition of beta-catenin degradation in an intact Axin1 complex. Cell. 2012;149:1245-1256.

    Not in our library10.1016/j.cell.2012.05.002

  11. 11.

    MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev. Cell. 2009;17:9-26.

    Not in our library10.1016/j.devcel.2009.06.016

  12. 12.

    Gao ZH, Seeling JM, Hill V, Yochum A, Virshup DM. Casein kinase I phosphorylates and destabilizes the beta-catenin degradation complex. Proc. Natl Acad. Sci. USA. 2002;99:1182-1187.

    Not in our library10.1073/pnas.032468199

  13. 13.

    Ha NC, Tonozuka T, Stamos JL, Choi HJ, Weis WI. Mechanism of phosphorylation-dependent binding of APC to beta-catenin and its role in beta-catenin degradation. Mol. Cell. 2004;15:511-521.

    Not in our library10.1016/j.molcel.2004.08.010

  14. 14.

    Liu C, et al. Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell. 2002;108:837-847.

    Not in our library10.1016/s0092-8674(02)00685-2

  15. 15.

    Stamos JL, Weis WI. The beta-catenin destruction complex. Cold Spring Harb. Perspect. Biol. 2013;5:a007898.

    Not in our library10.1101/cshperspect.a007898

  16. 16.
    Inhibition of GSK3 Phosphorylation of β-Catenin via Phosphorylated PPPSPXS Motifs of Wnt Coreceptor LRP6 · 2009
    No notice
  17. 17.

    Schatoff EM, Leach BI, Dow LE. Wnt signaling and colorectal cancer. Curr. Colorectal Cancer Rep. 2017;13:101-110.

    Not in our library10.1007/s11888-017-0354-9

  18. 18.

    White BD, Chien AJ, Dawson DW. Dysregulation of Wnt/beta-catenin signaling in gastrointestinal cancers. Gastroenterology. 2012;142:219-232.

    Not in our library10.1053/j.gastro.2011.12.001

  19. 19.

    Kwong LN, Dove WF. APC and its modifiers in colon cancer. Adv. Exp. Med. Biol. 2009;656:85-106.

    Not in our library10.1007/978-1-4419-1145-2_8

  20. 20.
    APC mutations in sporadic colorectal tumors: A mutational “hotspot” and interdependence of the “two hits” · 2000
    Not checked
  21. 21.
    A multigene mutation classification of 468 colorectal cancers reveals a prognostic role for APC · 2016
    No notice
  22. 22.

    Groden J, et al. Identification and characterization of the familial adenomatous polyposis coli gene. Cell. 1991;66:589-600.

    Not in our library10.1016/0092-8674(81)90021-0

  23. 23.

    Kimelman D, Xu W. beta-catenin destruction complex: insights and questions from a structural perspective. Oncogene. 2006;25:7482-7491.

    Not in our library10.1038/sj.onc.1210055

  24. 24.

    Xing Y, et al. Crystal structure of a beta-catenin/APC complex reveals a critical role for APC phosphorylation in APC function. Mol. Cell. 2004;15:523-533.

    Not in our library10.1016/j.molcel.2004.08.001

  25. 25.

    Cadigan K. M., Waterman M. L. TCF/LEFs and Wnt Signaling in the Nucleus. Cold Spring Harbor Perspectives in Biology. 2012;4(11):a007906-a007906.

    Not in our library10.1101/cshperspect.a007906

  26. 26.
    Target genes of β-catenin–T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas · 1999
    Not checked
  27. 27.

    Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61:759-767.

    Not in our library10.1016/0092-8674(90)90186-i

  28. 28.

    Hashimoto K, et al. Cellular context-dependent consequences of Apc mutations on gene regulation and cellular behavior. Proc. Natl Acad. Sci. USA. 2017;114:758-763.

    Not in our library10.1073/pnas.1614197114

  29. 29.

    Worm J, Christensen C, Gronbaek K, Tulchinsky E, Guldberg P. Genetic and epigenetic alterations of the APC gene in malignant melanoma. Oncogene. 2004;23:5215-5226.

    Not in our library10.1038/sj.onc.1207647

  30. 30.

    Moseley JB, et al. Regulated binding of adenomatous polyposis coli protein to actin. J. Biol. Chem. 2007;282:12661-12668.

    Not in our library10.1074/jbc.m610615200

  31. 31.

    Okada K, et al. Adenomatous polyposis coli protein nucleates actin assembly and synergizes with the formin mDia1. J. Cell Biol. 2010;189:1087-1096.

    Not in our library10.1083/jcb.201001016

  32. 32.

    Schlessinger K, McManus EJ, Hall A. Cdc42 and noncanonical Wnt signal transduction pathways cooperate to promote cell polarity. J. Cell Biol. 2007;178:355-361.

    Not in our library10.1083/jcb.200701083

  33. 33.

    Watanabe T, et al. Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration. Dev. Cell. 2004;7:871-883.

    Not in our library10.1016/j.devcel.2004.10.017

  34. 34.

    Caldwell CM, Kaplan KB. The role of APC in mitosis and in chromosome instability. Adv. Exp. Med. Biol. 2009;656:51-64.

    Not in our library10.1007/978-1-4419-1145-2_5

  35. 35.

    Hulsken J, Birchmeier W, Behrens J, E-cadherin APC. compete for the interaction with beta-catenin and the cytoskeleton. J. Cell Biol. 1994;127:2061-2069.

    Not in our library10.1083/jcb.127.6.2061

  36. 36.

    Juanes MA, et al. Adenomatous polyposis coli nucleates actin assembly to drive cell migration and microtubule-induced focal adhesion turnover. J. Cell Biol. 2017;216:2859-2875.

    Not in our library10.1083/jcb.201702007

  37. 37.

    Rusan NM, et al. CIN: reviewing roles for APC in chromosome instability. J. Cell Biol. 2008;181:719-726.

    Not in our library10.1083/jcb.200802107

  38. 38.
    E‐Cadherin/ β ‐Catenin Complex and the Epithelial Barrier · 2011
    No notice
  39. 39.

    Jung YS, et al. TMEM9 promotes intestinal tumorigenesis through vacuolar-ATPase-activated Wnt/beta-catenin signalling. Nat. Cell Biol. 2018;20:1421-1433.

    Not in our library10.1038/s41556-018-0219-8

  40. 40.

    Voloshanenko O, et al. Wnt secretion is required to maintain high levels of Wnt activity in colon cancer cells. Nat. Commun. 2013;4:2610.

    Not in our library10.1038/ncomms3610

  41. 41.

    Kishida M, et al. Axin prevents Wnt-3a-induced accumulation of beta-catenin. Oncogene. 1999;18:979-985.

    Not in our library10.1038/sj.onc.1202388

  42. 42.

    Luo W, Lin SC. Axin: a master scaffold for multiple signaling pathways. Neurosignals. 2004;13:99-113.

    Not in our library10.1159/000076563

  43. 43.

    Mazzoni SM, Fearon ER. AXIN1 and AXIN2 variants in gastrointestinal cancers. Cancer Lett. 2014;355:1-8.

    Not in our library10.1016/j.canlet.2014.09.018

  44. 44.

    Salahshor S, Woodgett JR. The links between axin and carcinogenesis. J. Clin. Pathol. 2005;58:225-236.

    Not in our library10.1136/jcp.2003.009506

  45. 45.

    Haraguchi K, et al. Ajuba negatively regulates the Wnt signaling pathway by promoting GSK-3beta-mediated phosphorylation of beta-catenin. Oncogene. 2008;27:274-284.

    Not in our library10.1038/sj.onc.1210644

  46. 46.

    Kim NG, Xu C, Gumbiner BM. Identification of targets of the Wnt pathway destruction complex in addition to beta-catenin. Proc. Natl Acad. Sci. USA. 2009;106:5165-5170.

    Not in our library10.1073/pnas.0810185106

  47. 47.

    Dajani R, et al. Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex. EMBO J. 2003;22:494-501.

    Not in our library10.1093/emboj/cdg068

  48. 48.

    Ikeda S, et al. Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. EMBO J. 1998;17:1371-1384.

    Not in our library10.1093/emboj/17.5.1371

  49. 49.

    Kim SE, et al. Wnt stabilization of beta-catenin reveals principles for morphogen receptor-scaffold assemblies. Science. 2013;340:867-870.

    Not in our library10.1126/science.1232389

  50. 50.

    Willert K, Shibamoto S, Nusse R. Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex. Genes Dev. 1999;13:1768-1773.

    Not in our library10.1101/gad.13.14.1768

  51. 51.

    Zeng X, et al. A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation. Nature. 2005;438:873-877.

    Not in our library10.1038/nature04185

  52. 52.

    MacDonald B. T., He X. Frizzled and LRP5/6 Receptors for Wnt/ -Catenin Signaling. Cold Spring Harbor Perspectives in Biology. 2012;4(12):a007880-a007880.

    Not in our library10.1101/cshperspect.a007880

  53. 53.

    Zeng X, et al. Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions. Development. 2008;135:367-375.

    Not in our library10.1242/dev.013540

  54. 54.

    He X, Semenov M, Tamai K, Zeng X. LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way. Development. 2004;131:1663-1677.

    Not in our library10.1242/dev.01117

  55. 55.
    Direct Inhibition of GSK3β by the Phosphorylated Cytoplasmic Domain of LRP6 in Wnt/β-Catenin Signaling · 2008
    No notice
  56. 56.
    Structural basis of GSK-3 inhibition by N-terminal phosphorylation and by the Wnt receptor LRP6 · 2014
    No notice
  57. 57.

    Kishida S, et al. DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate beta-catenin stability. Mol. Cell Biol. 1999;19:4414-4422.

    Not in our library10.1128/mcb.19.6.4414

  58. 58.

    Herr P, Basler K. Porcupine-mediated lipidation is required for Wnt recognition by Wls. Dev. Biol. 2012;361:392-402.

    Not in our library10.1016/j.ydbio.2011.11.003

  59. 59.

    Zimmerli D, Hausmann G, Cantu C, Basler K. Pharmacological interventions in the Wnt pathway: inhibition of Wnt secretion versus disrupting the protein-protein interfaces of nuclear factors. Br. J. Pharm. 2017;174:4600-4610.

    Not in our library10.1111/bph.13864

  60. 60.

    Liu J, et al. An integrated TCGA pan-cancer clinical data resource to drive high-quality survival outcome analytics. Cell. 2018;173:400-416 e411.

    Not in our library10.1016/j.cell.2018.02.052

  61. 61.

    Grigoryan T, Wend P, Klaus A, Birchmeier W. Deciphering the function of canonical Wnt signals in development and disease: conditional loss- and gain-of-function mutations of beta-catenin in mice. Genes Dev. 2008;22:2308-2341.

    Not in our library10.1101/gad.1686208

  62. 62.

    Harada N, et al. Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene. EMBO J. 1999;18:5931-5942.

    Not in our library10.1093/emboj/18.21.5931

  63. 63.

    Kim S, Jeong S. Mutation hotspots in the beta-catenin gene: lessons from the human cancer genome databases. Mol. Cells. 2019;42:8-16.

    Not in our library10.14348/molcells.2018.0436

  64. 64.
    TCF/LEF Transcription Factors: An Update from the Internet Resources · 2016
    No notice
  65. 65.

    Orsulic S, Peifer M. An in vivo structure-function study of armadillo, the beta-catenin homologue, reveals both separate and overlapping regions of the protein required for cell adhesion and for wingless signaling. J. Cell Biol. 1996;134:1283-1300.

    Not in our library10.1083/jcb.134.5.1283

  66. 66.

    van de Wetering M, et al. Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell. 1997;88:789-799.

    Not in our library10.1016/s0092-8674(00)81925-x

  67. 67.

    Huber AH, Weis WI. The structure of the beta-catenin/E-cadherin complex and the molecular basis of diverse ligand recognition by beta-catenin. Cell. 2001;105:391-402.

    Not in our library10.1016/s0092-8674(01)00330-0

  68. 68.

    Valenta T, Hausmann G, Basler K. The many faces and functions of beta-catenin. EMBO J. 2012;31:2714-2736.

    Not in our library10.1038/emboj.2012.150

  69. 69.

    Amit S, et al. Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. Genes Dev. 2002;16:1066-1076.

    Not in our library10.1101/gad.230302

  70. 70.

    Machin P, et al. CTNNB1 mutations and beta-catenin expression in endometrial carcinomas. Hum. Pathol. 2002;33:206-212.

    Not in our library10.1053/hupa.2002.30723

  71. 71.

    Liu J, et al. Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc. Natl Acad. Sci. USA. 2013;110:20224-20229.

    Not in our library10.1073/pnas.1314239110

  72. 72.

    Madan B, et al. Wnt addiction of genetically defined cancers reversed by PORCN inhibition. Oncogene. 2016;35:2197-2207.

    Not in our library10.1038/onc.2015.280

  73. 73.

    Mullighan CG, et al. CREBBP mutations in relapsed acute lymphoblastic leukaemia. Nature. 2011;471:235-239.

    Not in our library10.1038/nature09727

  74. 74.

    Wang X, et al. The development of highly potent inhibitors for porcupine. J. Med Chem. 2013;56:2700-2704.

    Not in our library10.1021/jm400159c

  75. 75.

    Madan B, et al. Bone loss from Wnt inhibition mitigated by concurrent alendronate therapy. Bone Res. 2018;6:17.

    Not in our library10.1038/s41413-018-0017-8

  76. 76.

    Cheng CK, et al. Secreted-frizzled related protein 1 is a transcriptional repression target of the t(8;21) fusion protein in acute myeloid leukemia. Blood. 2011;118:6638-6648.

    Not in our library10.1182/blood-2011-05-354712

  77. 77.

    Shi Y, He B, You L, Jablons DM. Roles of secreted frizzled-related proteins in cancer. Acta Pharm. Sin. 2007;28:1499-1504.

    Not in our library10.1111/j.1745-7254.2007.00692.x

  78. 78.

    Uren A, et al. Secreted frizzled-related protein-1 binds directly to Wingless and is a biphasic modulator of Wnt signaling. J. Biol. Chem. 2000;275:4374-4382.

    Not in our library10.1074/jbc.275.6.4374

  79. 79.

    Gonzalez DM, Medici D. Signaling mechanisms of the epithelial-mesenchymal transition. Sci. Signal. 2014;7:re8.

    Not in our library10.1126/scisignal.2005189

  80. 80.

    Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat. Rev. Mol. Cell Biol. 2014;15:178-196.

    Not in our library10.1038/nrm3758

  81. 81.

    Fischer MM, et al. WNT antagonists exhibit unique combinatorial antitumor activity with taxanes by potentiating mitotic cell death. Sci. Adv. 2017;3:e1700090.

    Not in our library10.1126/sciadv.1700090

  82. 82.

    Jimeno A, et al. A first-in-human phase i study of the anticancer stem cell agent ipafricept (OMP-54F28), a decoy receptor for Wnt ligands, in patients with advanced solid tumors. Clin. Cancer Res. 2017;23:7490-7497.

    Not in our library10.1158/1078-0432.ccr-17-2157

  83. 83.

    Moore KN, et al. A phase 1b dose escalation study of ipafricept (OMP54F28) in combination with paclitaxel and carboplatin in patients with recurrent platinum-sensitive ovarian cancer. Gynecol. Oncol. 2019;154:294-301.

    Not in our library10.1016/j.ygyno.2019.04.001

  84. 84.

    Giraudet AL, et al. A first-in-human study investigating biodistribution, safety and recommended dose of a new radiolabeled MAb targeting FZD10 in metastatic synovial sarcoma patients. BMC Cancer. 2018;18:646.

    Not in our library10.1186/s12885-018-4544-x

  85. 85.

    Lu D, et al. Salinomycin inhibits Wnt signaling and selectively induces apoptosis in chronic lymphocytic leukemia cells. Proc. Natl Acad. Sci. USA. 2011;108:13253-13257.

    Not in our library10.1073/pnas.1110431108

  86. 86.

    Tumova L, et al. Monensin inhibits canonical Wnt signaling in human colorectal cancer cells and suppresses tumor growth in multiple intestinal neoplasia mice. Mol. Cancer Ther. 2014;13:812-822.

    Not in our library10.1158/1535-7163.mct-13-0625

  87. 87.

    Zhu Y, et al. Rottlerin as a novel chemotherapy agent for adrenocortical carcinoma. Oncotarget. 2017;8:22825-22834.

    Not in our library10.18632/oncotarget.15221

  88. 88.

    Li Y, et al. Multi-targeted therapy of cancer by niclosamide: a new application for an old drug. Cancer Lett. 2014;349:8-14.

    Not in our library10.1016/j.canlet.2014.04.003

  89. 89.
    Salinomycin as a Drug for Targeting Human Cancer Stem Cells · 2012
    No notice
  90. 90.

    Huang SM, et al. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature. 2009;461:614-620.

    Not in our library10.1038/nature08356

  91. 91.
    Regulation of Wnt/β‐catenin signalling by tankyrase‐dependent poly(ADP‐ribosyl)ation and scaffolding · 2017
    No notice
  92. 92.

    Morrone S, Cheng Z, Moon RT, Cong F, Xu W. Crystal structure of a Tankyrase-Axin complex and its implications for Axin turnover and Tankyrase substrate recruitment. Proc. Natl Acad. Sci. USA. 2012;109:1500-1505.

    Not in our library10.1073/pnas.1116618109

  93. 93.

    Lau T, et al. A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven colorectal tumor growth. Cancer Res. 2013;73:3132-3144.

    Not in our library10.1158/0008-5472.can-12-4562

  94. 94.

    Menon M, et al. A novel tankyrase inhibitor, MSC2504877, enhances the effects of clinical CDK4/6 inhibitors. Sci. Rep. 2019;9:201.

    Not in our library10.1038/s41598-018-36447-4

  95. 95.

    Mizutani A, et al. RK-287107, a potent and specific tankyrase inhibitor, blocks colorectal cancer cell growth in a preclinical model. Cancer Sci. 2018;109:4003-4014.

    Not in our library10.1111/cas.13805

  96. 96.

    Thorne CA, et al. Small-molecule inhibition of Wnt signaling through activation of casein kinase 1alpha. Nat. Chem. Biol. 2010;6:829-836.

    Not in our library10.1038/nchembio.453

  97. 97.

    He TC, et al. Identification of c-MYC as a target of the APC pathway. Science. 1998;281:1509-1512.

    Not in our library10.1126/science.281.5382.1509

  98. 98.

    Jho EH, et al. Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol. Cell Biol. 2002;22:1172-1183.

    Not in our library10.1128/mcb.22.4.1172-1183.2002

  99. 99.

    Tetsu O, McCormick F. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature. 1999;398:422-426.

    Not in our library10.1038/18884

  100. 100.

    Wielenga VJ, et al. Expression of CD44 in Apc and Tcf mutant mice implies regulation by the WNT pathway. Am. J. Pathol. 1999;154:515-523.

    Not in our library10.1016/s0002-9440(10)65297-2

  101. 101.

    Wolf D, Rodova M, Miska EA, Calvet JP, Kouzarides T. Acetylation of beta-catenin by CREB-binding protein (CBP). J. Biol. Chem. 2002;277:25562-25567.

    Not in our library10.1074/jbc.m201196200

  102. 102.
    β-Catenin Cooperates with CREB Binding Protein to Promote the Growth of Tumor Cells · 2017
    Not checked
  103. 103.

    Takemaru KI, Moon RT. The transcriptional coactivator CBP interacts with beta-catenin to activate gene expression. J. Cell Biol. 2000;149:249-254.

    Not in our library10.1083/jcb.149.2.249

  104. 104.

    Yang K, et al. The evolving roles of canonical WNT signaling in stem cells and tumorigenesis: implications in targeted cancer therapies. Lab Invest. 2016;96:116-136.

    Not in our library10.1038/labinvest.2015.144

  105. 105.

    Cantù Claudio, Pagella Pierfrancesco, Shajiei Tania D., Zimmerli Dario, Valenta Tomas, Hausmann George, Basler Konrad, Mitsiadis Thimios A. A cytoplasmic role of Wnt/β-catenin transcriptional cofactors Bcl9, Bcl9l, and Pygopus in tooth enamel formation. Science Signaling. 2017;10(465):eaah4598.

    Not in our library10.1126/scisignal.aah4598

  106. 106.

    de la Roche M, Worm J, Bienz M. The function of BCL9 in Wnt/beta-catenin signaling and colorectal cancer cells. BMC Cancer. 2008;8:199.

    Not in our library10.1186/1471-2407-8-199

  107. 107.

    Feng M, et al. Pharmacological inhibition of beta-catenin/BCL9 interaction overcomes resistance to immune checkpoint blockades by modulating Treg cells. Sci. Adv. 2019;5:eaau5240.

    Not in our library10.1126/sciadv.aau5240

  108. 108.

    Lyou Y, Habowski AN, Chen GT, Waterman ML. Inhibition of nuclear Wnt signalling: challenges of an elusive target for cancer therapy. Br. J. Pharm. 2017;174:4589-4599.

    Not in our library10.1111/bph.13963

  109. 109.
    Direct Targeting of β-Catenin by a Small Molecule Stimulates Proteasomal Degradation and Suppresses Oncogenic Wnt/β-Catenin Signaling · 2016
    Not checked
  110. 110.

    Cantu C, et al. The Pygo2-H3K4me2/3 interaction is dispensable for mouse development and Wnt signaling-dependent transcription. Development. 2013;140:2377-2386.

    Not in our library10.1242/dev.093591

  111. 111.

    Hao HX, et al. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature. 2012;485:195-200.

    Not in our library10.1038/nature11019

  112. 112.

    Horst D, et al. Differential WNT activity in colorectal cancer confers limited tumorigenic potential and is regulated by MAPK signaling. Cancer Res. 2012;72:1547-1556.

    Not in our library10.1158/0008-5472.can-11-3222

  113. 113.

    Jung YS, Jun S, Lee SH, Sharma A, Park JI. Wnt2 complements Wnt/beta-catenin signaling in colorectal cancer. Oncotarget. 2015;6:37257-37268.

    Not in our library10.18632/oncotarget.6133

  114. 114.

    Jung YS, et al. Deregulation of CRAD-controlled cytoskeleton initiates mucinous colorectal cancer via beta-catenin. Nat. Cell Biol. 2018;20:1303-1314.

    Not in our library10.1038/s41556-018-0215-z

  115. 115.

    Koo BK, et al. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature. 2012;488:665-669.

    Not in our library10.1038/nature11308

  116. 116.

    Jung HY, et al. PAF and EZH2 induce Wnt/beta-catenin signaling hyperactivation. Mol. Cell. 2013;52:193-205.

    Not in our library10.1016/j.molcel.2013.08.028

  117. 117.

    Kim MJ, et al. PAF-Myc-controlled cell stemness is required for intestinal regeneration and tumorigenesis. Dev. Cell. 2018;44:582-596 e584.

    Not in our library10.1016/j.devcel.2018.02.010

  118. 118.

    He B, et al. Blockade of Wnt-1 signaling induces apoptosis in human colorectal cancer cells containing downstream mutations. Oncogene. 2005;24:3054-3058.

    Not in our library10.1038/sj.onc.1208511

  119. 119.

    Benary U, Kofahl B, Hecht A, Wolf J. Modeling Wnt/beta-catenin target gene expression in APC and Wnt gradients under wild type and mutant conditions. Front Physiol. 2013;4:21.

    Not in our library10.3389/fphys.2013.00021

  120. 120.

    Goentoro L, Kirschner MW. Evidence that fold-change, and not absolute level, of beta-catenin dictates Wnt signaling. Mol. Cell. 2009;36:872-884.

    Not in our library10.1016/j.molcel.2009.11.017

  121. 121.
    Comprehensive analysis of β-catenin target genes in colorectal carcinoma cell lines with deregulated Wnt/β-catenin signaling · 2014
    No notice
  122. 122.

    Scarborough HA, et al. AZ1366: an inhibitor of tankyrase and the canonical Wnt pathway that limits the persistence of non-small cell lung cancer cells following EGFR inhibition. Clin. Cancer Res. 2017;23:1531-1541.

    Not in our library10.1158/1078-0432.ccr-16-1179

  123. 123.

    Phelps RA, et al. A two-step model for colon adenoma initiation and progression caused by APC loss. Cell. 2009;137:623-634.

    Not in our library10.1016/j.cell.2009.02.037

  124. 124.

    Johnson DE, Ostrowski P, Jaumouille V, Grinstein S. The position of lysosomes within the cell determines their luminal pH. J. Cell Biol. 2016;212:677-692.

    Not in our library10.1083/jcb.201507112

  125. 125.
    The curious case of vacuolar ATPase: regulation of signaling pathways · 2018
    No notice
  126. 126.

    Lawrence RE, Zoncu R. The lysosome as a cellular centre for signalling, metabolism and quality control. Nat. Cell Biol. 2019;21:133-142.

    Not in our library10.1038/s41556-018-0244-7

  127. 127.

    Chi C, et al. Disruption of lysosome function promotes tumor growth and metastasis in Drosophila. J. Biol. Chem. 2010;285:21817-21823.

    Not in our library10.1074/jbc.m110.131714

  128. 128.

    Hagemann AI, et al. In vivo analysis of formation and endocytosis of the Wnt/beta-catenin signaling complex in zebrafish embryos. J. Cell Sci. 2014;127:3970-3982.

    Not in our library10.1242/jcs.148767

  129. 129.

    Taelman VF, et al. Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes. Cell. 2010;143:1136-1148.

    Not in our library10.1016/j.cell.2010.11.034

  130. 130.

    Ding VW, Chen RH, McCormick F. Differential regulation of glycogen synthase kinase 3beta by insulin and Wnt signaling. J. Biol. Chem. 2000;275:32475-32481.

    Not in our library10.1074/jbc.m005342200

  131. 131.

    Saito-Diaz K, et al. APC inhibits ligand-independent Wnt signaling by the clathrin endocytic pathway. Dev. Cell. 2018;44:566-581 e568.

    Not in our library10.1016/j.devcel.2018.02.013

  132. 132.

    Cruciat CM, et al. Requirement of prorenin receptor and vacuolar H+-ATPase-mediated acidification for Wnt signaling. Science. 2010;327:459-463.

    Not in our library10.1126/science.1179802

  133. 133.

    Hermle T, Saltukoglu D, Grunewald J, Walz G, Simons M. Regulation of Frizzled-dependent planar polarity signaling by a V-ATPase subunit. Curr. Biol. 2010;20:1269-1276.

    Not in our library10.1016/j.cub.2010.05.057

  134. 134.

    Stransky L, Cotter K, Forgac M. The function of V-ATPases in cancer. Physiol. Rev. 2016;96:1071-1091.

    Not in our library10.1152/physrev.00035.2015

  135. 135.

    Cotter K, et al. The a3 isoform of subunit a of the vacuolar ATPase localizes to the plasma membrane of invasive breast tumor cells and is overexpressed in human breast cancer. Oncotarget. 2016;7:46142-46157.

    Not in our library10.18632/oncotarget.10063

  136. 136.

    Liu P, Chen H, Han L, Zou X, Shen W. Expression and role of V1A subunit of V-ATPases in gastric cancer cells. Int J. Clin. Oncol. 2015;20:725-735.

    Not in our library10.1007/s10147-015-0782-y

  137. 137.

    Ohta T, et al. Expression of 16 kDa proteolipid of vacuolar-type H(+)-ATPase in human pancreatic cancer. Br. J. Cancer. 1996;73:1511-1517.

    Not in our library10.1038/bjc.1996.285

  138. 138.

    Son SW, et al. Prognostic significance and function of the vacuolar H+-ATPase subunit V1E1 in esophageal squamous cell carcinoma. Oncotarget. 2016;7:49334-49348.

    Not in our library10.18632/oncotarget.10340

  139. 139.

    Inoue T, Forgac M. Cysteine-mediated cross-linking indicates that subunit C of the V-ATPase is in close proximity to subunits E and G of the V1 domain and subunit a of the V0 domain. J. Biol. Chem. 2005;280:27896-27903.

    Not in our library10.1074/jbc.m504890200

  140. 140.

    Marshansky V, Rubinstein JL, Gruber G. Eukaryotic V-ATPase: novel structural findings and functional insights. Biochim Biophys. Acta. 2014;1837:857-879.

    Not in our library10.1016/j.bbabio.2014.01.018

  141. 141.

    Kane PM. Disassembly and reassembly of the yeast vacuolar H(+)-ATPase in vivo. J. Biol. Chem. 1995;270:17025-17032.

    Not in our library

  142. 142.

    Kane PM. Regulation of V-ATPases by reversible disassembly. FEBS Lett. 2000;469:137-141.

    Not in our library10.1016/s0014-5793(00)01265-5

  143. 143.

    Rahman S, et al. Biochemical and biophysical properties of interactions between subunits of the peripheral stalk region of human V-ATPase. PLoS ONE. 2013;8:e55704.

    Not in our library10.1371/journal.pone.0055704

  144. 144.

    Sumner JP, et al. Regulation of plasma membrane V-ATPase activity by dissociation of peripheral subunits. J. Biol. Chem. 1995;270:5649-5653.

    Not in our library10.1074/jbc.270.10.5649

  145. 145.

    Avina-Zubieta JA, Galindo-Rodriguez G, Newman S, Suarez-Almazor ME, Russell AS. Long-term effectiveness of antimalarial drugs in rheumatic diseases. Ann. Rheum. Dis. 1998;57:582-587.

    Not in our library10.1136/ard.57.10.582

  146. 146.

    Bowman EJ, Graham LA, Stevens TH, Bowman BJ. The bafilomycin/concanamycin binding site in subunit c of the V-ATPases from Neurospora crassa and Saccharomyces cerevisiae. J. Biol. Chem. 2004;279:33131-33138.

    Not in our library10.1074/jbc.m404638200

  147. 147.

    Huss M, et al. Concanamycin A, the specific inhibitor of V-ATPases, binds to the V(o) subunit c. J. Biol. Chem. 2002;277:40544-40548.

    Not in our library10.1074/jbc.m207345200

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