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

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A basal-like breast cancer-specific role for SRF-IL6 in YAP-induced cancer stemness
T Kim; Suk Jin Yang; D Hwang; J Song; M Kim; S K Kim; K Kang; J Ahn; D Lee; M Y Kim; S Kim; J S Koo; S S Koh; Seon-Young Kim; D S Lim
Bibliographic Citation
Nature Communications, vol. 6, pp. 10186-10186
Publication Year
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.
Springer-Nature Pub Group
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