Breast cancer prevention by short-term inhibition of TGFβ signaling

Maša Alečković, Simona Cristea, Carlos R. Gil Del Alcazar, Pengze Yan, Lina Ding, Ethan D. Krop, Nicholas W. Harper, Ernesto Rojas Jimenez, Donghao Lu, Anushree C. Gulvady, Pierre Foidart, Marco Seehawer, Benedetto Diciaccio, Katherine C. Murphy, Jason Pyrdol, Jayati Anand, Kodie Garza, Kai W. Wucherpfennig, Rulla M. Tamimi, Franziska Michor () and Kornelia Polyak ()
Additional contact information
Maša Alečković: Dana-Farber Cancer Institute
Simona Cristea: Dana-Farber Cancer Institute
Carlos R. Gil Del Alcazar: Dana-Farber Cancer Institute
Pengze Yan: Dana-Farber Cancer Institute
Lina Ding: Dana-Farber Cancer Institute
Ethan D. Krop: Dana-Farber Cancer Institute
Nicholas W. Harper: Dana-Farber Cancer Institute
Ernesto Rojas Jimenez: Dana-Farber Cancer Institute
Donghao Lu: Brigham and Women’s Hospital
Anushree C. Gulvady: Dana-Farber Cancer Institute
Pierre Foidart: Dana-Farber Cancer Institute
Marco Seehawer: Dana-Farber Cancer Institute
Benedetto Diciaccio: Dana-Farber Cancer Institute
Katherine C. Murphy: Dana-Farber Cancer Institute
Jason Pyrdol: Brigham and Women’s Hospital
Jayati Anand: Dana-Farber Cancer Institute
Kodie Garza: Dana-Farber Cancer Institute
Kai W. Wucherpfennig: Dana-Farber Cancer Institute
Rulla M. Tamimi: Brigham and Women’s Hospital
Franziska Michor: Dana-Farber Cancer Institute
Kornelia Polyak: Dana-Farber Cancer Institute

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Cancer prevention has a profound impact on cancer-associated mortality and morbidity. We previously identified TGFβ signaling as a candidate regulator of mammary epithelial cells associated with breast cancer risk. Here, we show that short-term TGFBR inhibitor (TGFBRi) treatment of peripubertal ACI inbred and Sprague Dawley outbred rats induces lasting changes and prevents estrogen- and carcinogen-induced mammary tumors, respectively. We identify TGFBRi-responsive cell populations by single cell RNA-sequencing, including a unique epithelial subpopulation designated secretory basal cells (SBCs) with progenitor features. We detect SBCs in normal human breast tissues and find them to be associated with breast cancer risk. Interactome analysis identifies SBCs as the most interactive cell population and the main source of insulin-IGF signaling. Accordingly, inhibition of TGFBR and IGF1R decrease proliferation of organoid cultures. Our results reveal a critical role for TGFβ in regulating mammary epithelial cells relevant to breast cancer and serve as a proof-of-principle cancer prevention strategy.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-35043-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35043-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-35043-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().