Alečković M, Cristea S, Gil Del Alcazar CR, Yan P, Ding L, Krop ED, Harper NW, Rojas Jimenez E, Lu D, Gulvady AC, Foidart P, Seehawer M, Diciaccio B, Murphy KC, Pyrdol J, Anand J, Garza K, Wucherpfennig KW, Tamimi RM, Michor F, Polyak K. 2022. Breast cancer prevention by short-term inhibition of TGFβ signaling. Nature communications. 13(1):7558. Pubmed: 36476730 DOI:10.1038/s41467-022-35043-5


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.
© 2022. The Author(s).

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Franziska Michor uses the tools of theoretical evolutionary biology, applied mathematics, statistics, and computational biology to address important questions in cancer research.

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