University at Buffalo - The State University of New York
Skip to Content
ΔNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling. - PubMed - NCBI
Format

Send to

Choose Destination
See comment in PubMed Commons below
Nat Cell Biol. 2014 Oct;16(10):1004-15, 1-13. doi: 10.1038/ncb3040. Epub 2014 Sep 21.

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

Author information

1
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
2
1] Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA [2] Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
3
Department of Biochemistry, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, New York 14203, USA.
4
Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, 47014 Meldola, Italy.
5
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.
6
1] Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA [2] Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA.

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.

PMID:
25241036
PMCID:
PMC4183725
DOI:
10.1038/ncb3040
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Secondary source ID, Grant support

Publication types

MeSH terms

Substances

Secondary source ID

Grant support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center