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 language | English (US) |
|---|---|
| Pages (from-to) | E9580-E9589 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 115 |
| Issue number | 41 |
| DOIs | |
| State | Published - Oct 9 2018 |
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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 journal › Article
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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
C2 - 30257941
AN - SCOPUS:85054778110
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 -