EZH2 promotes expansion of breast tumor initiating cells through activation of RAF1-β-catenin signaling

Chun Ju Chang, Jer Yen Yang, Weiya Xia, Chun Te Chen, Xiaoming Xie, Chi-Hong Chao, Wendy A. Woodward, Jung Mao Hsu, Gabriel N. Hortobagyi, Mien Chie Hung*

*Corresponding author for this work

研究成果: Article同行評審

282 引文 斯高帕斯(Scopus)

摘要

It has been proposed that an aggressive secondary cancer stem cell population arises from a primary cancer stem cell population through acquisition of additional genetic mutations and drives cancer progression. Overexpression of Polycomb protein EZH2, essential in stem cell self-renewal, has been linked to breast cancer progression. However, critical mechanism linking increased EZH2 expression to BTIC (breast tumor initiating cell) regulation and cancer progression remains unclear. Here, we identify a mechanism in which EZH2 expression-mediated downregulation of DNA damage repair leads to accumulation of recurrent RAF1 gene amplification in BTICs, which activates p-ERK-β-catenin signaling to promote BTIC expansion. We further reveal that AZD6244, a clinical trial drug that inhibits RAF1-ERK signaling, could prevent breast cancer progression by eliminating BTICs.

原文English
頁(從 - 到)86-100
頁數15
期刊Cancer Cell
19
發行號1
DOIs
出版狀態Published - 18 一月 2011

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