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

87 Citations (Scopus)

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 - Jan 1 2014
Externally publishedYes

Fingerprint

Human Mammary Glands
Stem Cells
Neoplastic Stem Cells
Breast Neoplasms
Breast
Wnt Receptors
Adult Stem Cells
Neoplasms
Protein Isoforms
Transcription Factors

ASJC Scopus subject areas

  • Cell Biology

Cite this

Δnp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling. / Chakrabarti, Rumela; Wei, Yong; Hwang, Julie; Hang, Xiang; Andres Blanco, Mario; Choudhury, Abrar; Tiede, Benjamin; Romano, Rose Anne; Decoste, Christina; Mercatali, Laura; Ibrahim, Toni; Amadori, Dino; Kannan, Nagarajan; Eaves, Connie J.; Sinha, Satrajit; Kang, Yibin.

In: Nature Cell Biology, Vol. 16, No. 10, 01.01.2014, p. 1004-1015.

Research output: Contribution to journalArticle

Chakrabarti, R, Wei, Y, Hwang, J, Hang, X, Andres Blanco, M, Choudhury, A, Tiede, B, Romano, RA, Decoste, C, Mercatali, L, Ibrahim, T, Amadori, D, Kannan, N, Eaves, CJ, 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, vol. 16, no. 10, pp. 1004-1015. https://doi.org/10.1038/ncb3040
Chakrabarti, Rumela ; Wei, Yong ; Hwang, Julie ; Hang, Xiang ; Andres Blanco, Mario ; Choudhury, Abrar ; Tiede, Benjamin ; Romano, Rose Anne ; Decoste, Christina ; Mercatali, Laura ; Ibrahim, Toni ; Amadori, Dino ; Kannan, Nagarajan ; Eaves, Connie J. ; Sinha, Satrajit ; Kang, Yibin. / Δnp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling. In: Nature Cell Biology. 2014 ; Vol. 16, No. 10. pp. 1004-1015.
@article{634bab3b52c54d5fafb059732053316e,
title = "Δnp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling",
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.",
author = "Rumela Chakrabarti and Yong Wei and Julie Hwang and Xiang Hang and {Andres Blanco}, Mario and Abrar Choudhury and Benjamin Tiede and Romano, {Rose Anne} and Christina Decoste and Laura Mercatali and Toni Ibrahim and Dino Amadori and Nagarajan Kannan and Eaves, {Connie J.} and Satrajit Sinha and Yibin Kang",
year = "2014",
month = "1",
day = "1",
doi = "10.1038/ncb3040",
language = "English (US)",
volume = "16",
pages = "1004--1015",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Δnp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling

AU - Chakrabarti, Rumela

AU - Wei, Yong

AU - Hwang, Julie

AU - Hang, Xiang

AU - Andres Blanco, Mario

AU - Choudhury, Abrar

AU - Tiede, Benjamin

AU - Romano, Rose Anne

AU - Decoste, Christina

AU - Mercatali, Laura

AU - Ibrahim, Toni

AU - Amadori, Dino

AU - Kannan, Nagarajan

AU - Eaves, Connie J.

AU - Sinha, Satrajit

AU - Kang, Yibin

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84925298125&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925298125&partnerID=8YFLogxK

U2 - 10.1038/ncb3040

DO - 10.1038/ncb3040

M3 - Article

VL - 16

SP - 1004

EP - 1015

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 10

ER -