A Basal-like Breast Cancer-specific Role for SRF-IL6 in YAP-induced Cancer Stemness

Overview

Journal Nat Commun

Specialty Biology

Date 2015 Dec 17

PMID 26671411

Citations 101

Authors

Tackhoon Kim

Suk-Jin Yang

Daehee Hwang

Jinhoi Song

Minchul Kim

Sang Kyum Kim

Keunsoo Kang

Jaebum Ahn

Daeyoup Lee

Mi-Young Kim

Seyun Kim

Ja Seung Koo

Sang Seok Koh

Seon-Young Kim

Dae-Sik Lim

Affiliations

Soon will be listed here.

Abstract

The switch between stem/progenitor cell expansion and differentiation is critical for organ homeostasis. The mammalian Hippo pathway effector and oncoprotein YAP expands undifferentiated stem/progenitor cells in various tissues. However, the YAP-associated transcription factors and downstream targets underlying this stemness-promoting activity are poorly understood. Here we show that the SRF-IL6 axis is the critical mediator of YAP-induced stemness in mammary epithelial cells and breast cancer. Specifically, serum response factor (SRF)-mediated binding and recruitment of YAP to mammary stem cell (MaSC) signature-gene promoters induce numerous MaSC signature genes, among which the target interleukin (IL)-6 is critical for YAP-induced stemness. High SRF-YAP/TAZ expression is correlated with IL6-enriched MaSC/basal-like breast cancer (BLBC). Finally, we show that this high SRF expression enables YAP to more efficiently induce IL6 and stemness in BLBC compared with luminal-type breast cancer. Collectively, our results establish the importance of SRF-YAP-IL6 signalling in promoting MaSC-like properties in a BLBC-specific manner.

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