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Publication : ΔNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling.

First Author  Chakrabarti R Year  2014
Journal  Nat Cell Biol Volume  16
Issue  10 Pages  1004-15, 1-13
PubMed ID  25241036 Mgi Jnum  J:217708
Mgi Id  MGI:5615346 Doi  10.1038/ncb3040
Citation  Chakrabarti R, et al. (2014) DeltaNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling. Nat Cell Biol 16(10):1004-15, 1-13
abstractText  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 DeltaNp63 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 DeltaNp63 also governs tumour-initiating activity of the basal subtype of breast cancer. These findings establish DeltaNp63 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.
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