Δnp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling

Rumela Chakrabarti, Yong Wei, Julie Hwang, Xiang Hang, Mario Andres Blanco, Abrar Choudhury, Benjamin Tiede, Rose Anne Romano, Christina Decoste, Laura Mercatali, Toni Ibrahim, Dino Amadori, Nagarajan Kannan, Connie J. Eaves, Satrajit Sinha, Yibin Kang

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

Emerging evidence suggests that cancer is populated and maintained by tumour-initiating cells (TICs) with stem-like properties similar to those of adult tissue stem cells. Despite recent advances, the molecular regulatory mechanisms that may be shared between normal and malignant stem cells remain poorly understood. Here we show that the ΔNp63 isoform of the Trp63 transcription factor promotes normal mammary stem cell (MaSC) activity by increasing the expression of the Wnt receptor Fzd7, thereby enhancing Wnt signalling. Importantly, Fzd7-dependent enhancement of Wnt signalling by ΔNp63 also governs tumour-initiating activity of the basal subtype of breast cancer. These findings establish ΔNp63 as a key regulator of stem cells in both normal and malignant mammary tissues and provide direct evidence that breast cancer TICs and normal MaSCs share common regulatory mechanisms.

Original languageEnglish (US)
Pages (from-to)1004-1015
Number of pages12
JournalNature cell biology
Volume16
Issue number10
DOIs
StatePublished - Oct 1 2014

All Science Journal Classification (ASJC) codes

  • Cell Biology

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    Chakrabarti, R., Wei, Y., Hwang, J., Hang, X., Andres Blanco, M., Choudhury, A., Tiede, B., Romano, R. A., Decoste, C., Mercatali, L., Ibrahim, T., Amadori, D., Kannan, N., Eaves, C. J., Sinha, S., & Kang, Y. (2014). Δnp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling. Nature cell biology, 16(10), 1004-1015. https://doi.org/10.1038/ncb3040