[HTML][HTML] A basal-like breast cancer-specific role for SRF–IL6 in YAP-induced cancer stemness

T Kim, SJ Yang, D Hwang, J Song, M Kim… - Nature …, 2015 - nature.com
T Kim, SJ Yang, D Hwang, J Song, M Kim, S Kyum Kim, K Kang, J Ahn, D Lee, M Kim, S Kim
Nature communications, 2015nature.com
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 …
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.
nature.com