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

2 Citations (Scopus)

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

Fingerprint

Cystatins
Triple Negative Breast Neoplasms
Estrogen Receptor beta
Neoplasm Metastasis
Therapeutics
Breast Neoplasms
Phenotype
Recurrence
Inhibition (Psychology)
Neoplasms
Proteins

ASJC Scopus subject areas

  • General

Cite this

ERβ-mediated induction of cystatins results in suppression of TGFβ signaling and inhibition of triple-negative breast cancer metastasis. / Reese, Jordan M.; Bruinsma, Elizabeth S.; Nelson, Adam W.; Chernukhin, Igor; Carroll, Jason S.; Li, Ying; Subramaniam, Malayannan; Suman, Vera Jean; Negron, Vivian; Monroe, David G; Ingle, James N.; Goetz, Matthew Philip; Hawse, John R.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 41, 09.10.2018, p. E9580-E9589.

Research output: Contribution to journalArticle

Reese, Jordan M. ; Bruinsma, Elizabeth S. ; Nelson, Adam W. ; Chernukhin, Igor ; Carroll, Jason S. ; Li, Ying ; Subramaniam, Malayannan ; Suman, Vera Jean ; Negron, Vivian ; Monroe, David G ; Ingle, James N. ; Goetz, Matthew Philip ; Hawse, John R. / ERβ-mediated induction of cystatins results in suppression of TGFβ signaling and inhibition of triple-negative breast cancer metastasis. In: Proceedings of the National Academy of Sciences of the United States of America. 2018 ; Vol. 115, No. 41. pp. E9580-E9589.
@article{c5893b7518d548ad8a3b87d8c878aad9,
title = "ERβ-mediated induction of cystatins results in suppression of TGFβ signaling and inhibition of triple-negative breast cancer metastasis",
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.",
author = "Reese, {Jordan M.} and Bruinsma, {Elizabeth S.} and Nelson, {Adam W.} and Igor Chernukhin and Carroll, {Jason S.} and Ying Li and Malayannan Subramaniam and Suman, {Vera Jean} and Vivian Negron and Monroe, {David G} and Ingle, {James N.} and Goetz, {Matthew Philip} and Hawse, {John R}",
year = "2018",
month = "10",
day = "9",
doi = "10.1073/pnas.1807751115",
language = "English (US)",
volume = "115",
pages = "E9580--E9589",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "41",

}

TY - JOUR

T1 - ERβ-mediated induction of cystatins results in suppression of TGFβ signaling and inhibition of triple-negative breast cancer metastasis

AU - Reese, Jordan M.

AU - Bruinsma, Elizabeth S.

AU - Nelson, Adam W.

AU - Chernukhin, Igor

AU - Carroll, Jason S.

AU - Li, Ying

AU - Subramaniam, Malayannan

AU - Suman, Vera Jean

AU - Negron, Vivian

AU - Monroe, David G

AU - Ingle, James N.

AU - Goetz, Matthew Philip

AU - Hawse, John R

PY - 2018/10/9

Y1 - 2018/10/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85054778110&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054778110&partnerID=8YFLogxK

U2 - 10.1073/pnas.1807751115

DO - 10.1073/pnas.1807751115

M3 - Article

VL - 115

SP - E9580-E9589

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 41

ER -