Elf5 inhibits the epithelial-mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2

Rumela Chakrabarti, Julie Hwang, Mario Andres Blanco, Yong Wei, Martin Lukačišin, Rose Anne Romano, Kirsten Smalley, Song Liu, Qifeng Yang, Toni Ibrahim, Laura Mercatali, Dino Amadori, Bruce Haffty, Satrajit Sinha, Yibin Kang

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

The epithelial-mesenchymal transition (EMT) is a complex process that occurs during organogenesis and in cancer metastasis. Despite recent progress, the molecular pathways connecting the physiological and pathological functions of EMT need to be better defined. Here we show that the transcription factor Elf5, a key regulator of mammary gland alveologenesis, controls EMT in both mammary gland development and metastasis. We uncovered this role for Elf5 through analyses of Elf5 conditional knockout animals, various in vitro and in vivo models of EMT and metastasis, an MMTV-neu transgenic model of mammary tumour progression and clinical breast cancer samples. Furthermore, we demonstrate that Elf5 suppresses EMT by directly repressing the transcription of Snail2, a master regulator of mammary stem cells and a known inducer of EMT. These findings establish Elf5 not only as a key cell lineage regulator during normal mammary gland development, but also as a suppressor of EMT and metastasis in breast cancer.

Original languageEnglish (US)
Pages (from-to)1212-1222
Number of pages11
JournalNature Cell Biology
Volume14
Issue number11
DOIs
StatePublished - Nov 1 2012

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Epithelial-Mesenchymal Transition
Human Mammary Glands
Breast Neoplasms
Neoplasm Metastasis
Organogenesis
Cell Lineage
Breast
Transcription Factors
Stem Cells
Neoplasms

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Chakrabarti, R., Hwang, J., Andres Blanco, M., Wei, Y., Lukačišin, M., Romano, R. A., ... Kang, Y. (2012). Elf5 inhibits the epithelial-mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2. Nature Cell Biology, 14(11), 1212-1222. https://doi.org/10.1038/ncb2607
Chakrabarti, Rumela ; Hwang, Julie ; Andres Blanco, Mario ; Wei, Yong ; Lukačišin, Martin ; Romano, Rose Anne ; Smalley, Kirsten ; Liu, Song ; Yang, Qifeng ; Ibrahim, Toni ; Mercatali, Laura ; Amadori, Dino ; Haffty, Bruce ; Sinha, Satrajit ; Kang, Yibin. / Elf5 inhibits the epithelial-mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2. In: Nature Cell Biology. 2012 ; Vol. 14, No. 11. pp. 1212-1222.
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Chakrabarti, R, Hwang, J, Andres Blanco, M, Wei, Y, Lukačišin, M, Romano, RA, Smalley, K, Liu, S, Yang, Q, Ibrahim, T, Mercatali, L, Amadori, D, Haffty, B, Sinha, S & Kang, Y 2012, 'Elf5 inhibits the epithelial-mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2', Nature Cell Biology, vol. 14, no. 11, pp. 1212-1222. https://doi.org/10.1038/ncb2607

Elf5 inhibits the epithelial-mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2. / Chakrabarti, Rumela; Hwang, Julie; Andres Blanco, Mario; Wei, Yong; Lukačišin, Martin; Romano, Rose Anne; Smalley, Kirsten; Liu, Song; Yang, Qifeng; Ibrahim, Toni; Mercatali, Laura; Amadori, Dino; Haffty, Bruce; Sinha, Satrajit; Kang, Yibin.

In: Nature Cell Biology, Vol. 14, No. 11, 01.11.2012, p. 1212-1222.

Research output: Contribution to journalArticle

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AU - Smalley, Kirsten

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AU - Yang, Qifeng

AU - Ibrahim, Toni

AU - Mercatali, Laura

AU - Amadori, Dino

AU - Haffty, Bruce

AU - Sinha, Satrajit

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