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, Dae Sik Lim

Research output: Contribution to journalArticle

58 Citations (Scopus)

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.

Original languageEnglish
Article number10186
JournalNature communications
Volume6
DOIs
Publication statusPublished - 2015 Dec 16

Fingerprint

Serum Response Factor
stem cells
Stem cells
breast
serums
Interleukin-6
Stem Cells
cancer
Breast Neoplasms
Breast
Neoplasms
genes
Genes
signatures
interleukins
effectors
homeostasis
Oncogene Proteins
organs
Transcription Factors

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Kim, T., Yang, S. J., Hwang, D., Song, J., Kim, M., Kyum Kim, S., ... Lim, D. S. (2015). A basal-like breast cancer-specific role for SRF-IL6 in YAP-induced cancer stemness. Nature communications, 6, [10186]. https://doi.org/10.1038/ncomms10186
Kim, Tackhoon ; Yang, Suk Jin ; Hwang, Daehee ; Song, Jinhoi ; Kim, Minchul ; Kyum Kim, Sang ; Kang, Keunsoo ; Ahn, Jaebum ; Lee, Daeyoup ; Kim, Mi Young ; Kim, Seyun ; Seung Koo, Ja ; Seok Koh, Sang ; Kim, Seon Young ; Lim, Dae Sik. / A basal-like breast cancer-specific role for SRF-IL6 in YAP-induced cancer stemness. In: Nature communications. 2015 ; Vol. 6.
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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.",
author = "Tackhoon Kim and Yang, {Suk Jin} and Daehee Hwang and Jinhoi Song and Minchul Kim and {Kyum Kim}, Sang and Keunsoo Kang and Jaebum Ahn and Daeyoup Lee and Kim, {Mi Young} and Seyun Kim and {Seung Koo}, Ja and {Seok Koh}, Sang and Kim, {Seon Young} and Lim, {Dae Sik}",
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Kim, T, Yang, SJ, Hwang, D, Song, J, Kim, M, Kyum Kim, S, Kang, K, Ahn, J, Lee, D, Kim, MY, Kim, S, Seung Koo, J, Seok Koh, S, Kim, SY & Lim, DS 2015, 'A basal-like breast cancer-specific role for SRF-IL6 in YAP-induced cancer stemness', Nature communications, vol. 6, 10186. https://doi.org/10.1038/ncomms10186

A basal-like breast cancer-specific role for SRF-IL6 in YAP-induced cancer stemness. / Kim, Tackhoon; Yang, Suk Jin; Hwang, Daehee; Song, Jinhoi; Kim, Minchul; Kyum Kim, Sang; Kang, Keunsoo; Ahn, Jaebum; Lee, Daeyoup; Kim, Mi Young; Kim, Seyun; Seung Koo, Ja; Seok Koh, Sang; Kim, Seon Young; Lim, Dae Sik.

In: Nature communications, Vol. 6, 10186, 16.12.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A basal-like breast cancer-specific role for SRF-IL6 in YAP-induced cancer stemness

AU - Kim, Tackhoon

AU - Yang, Suk Jin

AU - Hwang, Daehee

AU - Song, Jinhoi

AU - Kim, Minchul

AU - Kyum Kim, Sang

AU - Kang, Keunsoo

AU - Ahn, Jaebum

AU - Lee, Daeyoup

AU - Kim, Mi Young

AU - Kim, Seyun

AU - Seung Koo, Ja

AU - Seok Koh, Sang

AU - Kim, Seon Young

AU - Lim, Dae Sik

PY - 2015/12/16

Y1 - 2015/12/16

N2 - 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.

AB - 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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