title: A basal-like breast cancer-specific role for SRF-IL6 in YAP-induced cancer stemness.
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.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.|National Creative Research Center for Cell Division and Differentiation, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Tackhoon
authors.initials: T
authors.lastname: Kim
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
authors.forename: Suk-Jin
authors.initials: SJ
authors.lastname: Yang
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.|National Creative Research Center for Cell Division and Differentiation, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.affiliation: Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
authors.forename: Jinhoi
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.|National Creative Research Center for Cell Division and Differentiation, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Minchul
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Sang
authors.initials: S
authors.lastname: Kyum Kim
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Keunsoo
authors.initials: K
authors.lastname: Kang
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.|National Creative Research Center for Cell Division and Differentiation, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Jaebum
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Daeyoup
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Seyun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Ja
authors.initials: J
authors.lastname: Seung Koo
authors.affiliation: Department of Biological Sciences, Dong-A University, Busan 604-714, Korea.
authors.forename: Sang
authors.initials: S
authors.lastname: Seok Koh
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Dae-Sik
authors.initials: DS
authors.lastname: Lim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism*; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D046228:Microarray Analysis; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D026362:Serum Response Factor / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism; D046888:Tissue Array Analysis; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C508600:IL6 protein, human; D015850:Interleukin-6; D010750:Phosphoproteins; C476858:SRF protein, human; D026362:Serum Response Factor; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human