ERβ-mediated Induction of Cystatins Results in Suppression of TGFβ Signaling and Inhibition of Triple-negative Breast Cancer Metastasis

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2018 Sep 28

PMID 30257941

Citations 34

Authors

Jordan M Reese

Elizabeth S Bruinsma

Adam W Nelson

Igor Chernukhin

Jason S Carroll

Ying Li

Malayannan Subramaniam

Vera J Suman

Vivian Negron

David G Monroe

James N Ingle

Matthew P Goetz

John R Hawse

Affiliations

Soon will be listed here.

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.

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