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Breast cancer prevention by short-term inhibition of TGFβ signaling

Author

Listed:
  • Maša Alečković

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Simona Cristea

    (Dana-Farber Cancer Institute
    Harvard University
    Harvard T. H. Chan School of Public Health)

  • Carlos R. Gil Del Alcazar

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Pengze Yan

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Lina Ding

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Ethan D. Krop

    (Dana-Farber Cancer Institute)

  • Nicholas W. Harper

    (Dana-Farber Cancer Institute)

  • Ernesto Rojas Jimenez

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Donghao Lu

    (Brigham and Women’s Hospital
    Harvard T. H. Chan School of Public Health)

  • Anushree C. Gulvady

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Pierre Foidart

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Marco Seehawer

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital
    Harvard Medical School)

  • 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
    Harvard Medical School)

  • Rulla M. Tamimi

    (Brigham and Women’s Hospital
    Harvard T. H. Chan School of Public Health)

  • Franziska Michor

    (Dana-Farber Cancer Institute
    Harvard University
    Harvard T. H. Chan School of Public Health
    Dana-Farber Cancer Institute)

  • Kornelia Polyak

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital
    Harvard Medical School
    Dana-Farber Cancer Institute)

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.

Suggested Citation

  • 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 & , 2022. "Breast cancer prevention by short-term inhibition of TGFβ signaling," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35043-5
    DOI: 10.1038/s41467-022-35043-5
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    References listed on IDEAS

    as
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