Circular RNA-encoded Oncogenic E-cadherin Variant Promotes Glioblastoma Tumorigenicity Through Activation of EGFR-STAT3 Signalling

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2021 Mar 5

PMID 33664496

Citations 181

Authors

Xinya Gao

Xin Xia

Fanying Li

Maolei Zhang

Huangkai Zhou

Xujia Wu

Jian Zhong

Zheng Zhao

Kun Zhao

Dawei Liu

Feizhe Xiao

Qiang Xu

Tao Jiang

Bo Li

Shi-Yuan Cheng

Nu Zhang

Affiliations

Soon will be listed here.

Abstract

Activated EGFR signalling drives tumorigenicity in 50% of glioblastoma (GBM). However, EGFR-targeting therapy has proven ineffective in treating patients with GBM, indicating that there is redundant EGFR activation. Circular RNAs are covalently closed RNA transcripts that are involved in various physiological and pathological processes. Herein, we report an additional activation mechanism of EGFR signalling in GBM by an undescribed secretory E-cadherin protein variant (C-E-Cad) encoded by a circular E-cadherin (circ-E-Cad) RNA through multiple-round open reading frame translation. C-E-Cad is overexpressed in GBM and promotes glioma stem cell tumorigenicity. C-E-Cad activates EGFR independent of EGF through association with the EGFR CR2 domain using a unique 14-amino-acid carboxy terminus, thereby maintaining glioma stem cell tumorigenicity. Notably, inhibition of C-E-Cad markedly enhances the antitumour activity of therapeutic anti-EGFR strategies in GBM. Our results uncover a critical role of C-E-Cad in stimulating EGFR signalling and provide a promising approach for treating EGFR-driven GBM.

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