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ΔNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling.
- Source :
-
Nature cell biology [Nat Cell Biol] 2014 Oct; Vol. 16 (10), pp. 1004-15, 1-13. Date of Electronic Publication: 2014 Sep 21. - Publication Year :
- 2014
-
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.
- Subjects :
- Animals
Blotting, Western
Breast Neoplasms genetics
Breast Neoplasms pathology
Cell Line, Tumor
Epithelial Cells metabolism
Frizzled Receptors genetics
Gene Expression Regulation, Neoplastic
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
Humans
Interleukin Receptor Common gamma Subunit deficiency
Interleukin Receptor Common gamma Subunit genetics
Mammary Glands, Animal cytology
Mammary Glands, Animal metabolism
Mammary Glands, Human cytology
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, Knockout
Mice, SCID
Mice, Transgenic
Microscopy, Confocal
Neoplastic Stem Cells metabolism
Neoplastic Stem Cells pathology
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
Stem Cells cytology
Transcription Factors genetics
Transplantation, Heterologous
Tumor Suppressor Proteins genetics
Breast Neoplasms metabolism
Frizzled Receptors metabolism
Mammary Glands, Human metabolism
Stem Cells metabolism
Transcription Factors metabolism
Tumor Suppressor Proteins metabolism
Wnt Signaling Pathway
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4679
- Volume :
- 16
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Nature cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 25241036
- Full Text :
- https://doi.org/10.1038/ncb3040