ZEB1 regulates glioma stemness through LIF repression

The identification of a stem cell regulatory gene which is aberrantly expressed in glioma and associated with patient survival would increase the understanding of the role of glioma cancer stem cells (GCSCs) in the virulence of gliomas. Interrogating the genomes of over 4000 brain cancers we identified ZEB1 deletion in ~15% (grade II and III) and 50% of glioblastomas. Meta-analysis of ZEB1 copy number status in 2,988 cases of glioma revealed disruptive ZEB1 deletions associated with decreased survival. We identified ZEB1 binding sites within the LIF (stemness factor) promoter region, and demonstrate LIF repression by ZEB1. ZEB1 knockdown in GCSCs caused LIF induction commensurate with GCSC self-renewal and inhibition of differentiation. IFN-γ treatment to GCSCs induced ZEB1 expression, attenuating LIF activities. These findings implicate ZEB1 as a stem cell regulator in glioma which when deleted leads to increased stemness, tumorigenicity and shortened patient survival.

Abstract licence: CC BY-NC-ND

1. 35.

   COSMIC: exploring the world's knowledge of somatic mutations in human cancer · 2014

2. 38.

   The ZEB1 pathway links glioblastoma initiation, invasion and chemoresistance · 2013

40 more references, whose wording the paper’s licence keeps private.

• LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8+ T cell tumor-infiltration impairing anti-PD1 therapy · 2019

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.