A basal-like breast cancer-specific role for SRF-IL6 in YAP-induced cancer stemness.

Nat Commun 2015 Dec 16;6:10186. Epub 2015 Dec 16.

Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.

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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Source
http://dx.doi.org/10.1038/ncomms10186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703869PMC
December 2015
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