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

Jordan M. Reese, Elizabeth S. Bruinsma, Adam W. Nelson, Igor Chernukhin, Jason S. Carroll, Ying Li, Malayannan Subramaniam, Vera Jean Suman, Vivian Negron, David G Monroe, James N. Ingle, Matthew Philip Goetz, John R Hawse

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)E9580-E9589
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number41
DOIs
StatePublished - Oct 9 2018

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