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

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 and Dae-Sik Lim ()
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Tackhoon Kim: Korea Advanced Institute of Science and Technology
Suk-Jin Yang: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology
Daehee Hwang: Korea Advanced Institute of Science and Technology
Jinhoi Song: Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology
Minchul Kim: Korea Advanced Institute of Science and Technology
Sang Kyum Kim: Yonsei University College of Medicine
Keunsoo Kang: Korea Advanced Institute of Science and Technology
Jaebum Ahn: Korea Advanced Institute of Science and Technology
Daeyoup Lee: Korea Advanced Institute of Science and Technology
Mi-young Kim: Korea Advanced Institute of Science and Technology
Seyun Kim: Korea Advanced Institute of Science and Technology
Ja Seung Koo: Yonsei University College of Medicine
Sang Seok Koh: Dong-A University
Seon-Young Kim: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology
Dae-Sik Lim: Korea Advanced Institute of Science and Technology

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms10186

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