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ERβ-mediated induction of cystatins results in suppression of TGFβ signaling and inhibition of triple-negative breast cancer metastasis.

Accepted version
Peer-reviewed

Type

Article

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Authors

Reese, Jordan M 
Bruinsma, Elizabeth S 
Nelson, Adam W 
Chernukhin, Igor 
Carroll, Jason S 

Abstract

Triple-negative breast cancer (TNBC) accounts for a disproportionately high number of deaths due to a lack of targeted therapies and an increased likelihood of distant recurrence. Estrogen receptor beta (ERβ), a well-characterized tumor suppressor, is expressed in 30% of TNBCs, and its expression is associated with improved patient outcomes. We demonstrate that therapeutic activation of ERβ elicits potent anticancer effects in TNBC through the induction of a family of secreted proteins known as the cystatins, which function to inhibit canonical TGFβ signaling and suppress metastatic phenotypes both in vitro and in vivo. These data reveal the involvement of cystatins in suppressing breast cancer progression and highlight the value of ERβ-targeted therapies for the treatment of TNBC patients.

Description

Keywords

TGFβ, breast cancer, cystatin, estrogen receptor beta, metastasis, Animals, Cell Line, Tumor, Cystatins, Estrogen Receptor beta, Female, Humans, Mice, Signal Transduction, Transforming Growth Factor beta, Triple Negative Breast Neoplasms, Tumor Suppressor Proteins

Journal Title

Proc Natl Acad Sci U S A

Conference Name

Journal ISSN

0027-8424
1091-6490

Volume Title

115

Publisher

Proceedings of the National Academy of Sciences
Sponsorship
Medical Research Council (MR/L00156X/1)
Cancer Research UK (C14303/A17197)
Cancer Research UK (20411)