Estrogen Receptor β Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis

Sang Jun Han, Sung Yun Jung, San Pin Wu, Shannon Hawkins, Mi Jin Park, Satoru Kyo, Jun Qin, John P. Lydon, Sophia Y. Tsai, Ming Jer Tsai, Francesco J. Demayo, Bert W. O'Malley

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Summary Alterations in estrogen-mediated cellular signaling play an essential role in the pathogenesis of endometriosis. In addition to higher estrogen receptor (ER) β levels, enhanced ERβ activity was detected in endometriotic tissues, and the inhibition of enhanced ERβ activity by an ERβ-selective antagonist suppressed mouse ectopic lesion growth. Notably, gain of ERβ function stimulated the progression of endometriosis. As a mechanism to evade endogenous immune surveillance for cell survival, ERβ interacts with cellular apoptotic machinery in the cytoplasm to inhibit TNF-α-induced apoptosis. ERβ also interacts with components of the cytoplasmic inflammasome to increase interleukin-1β and thus enhance its cellular adhesion and proliferation properties. Furthermore, this gain of ERβ function enhances epithelial-mesenchymal transition signaling, thereby increasing the invasion activity of endometriotic tissues for establishment of ectopic lesions. Collectively, we reveal how endometrial tissue generated by retrograde menstruation can escape immune surveillance and develop into sustained ectopic lesions via gain of ERβ function.

Original languageEnglish (US)
Pages (from-to)960-974
Number of pages15
JournalCell
Volume163
Issue number4
DOIs
StatePublished - Nov 5 2015
Externally publishedYes

Fingerprint

Inflammasomes
Endometriosis
Estrogen Receptors
Apoptosis
Tissue
Menstruation Disturbances
Choristoma
Cell signaling
Epithelial-Mesenchymal Transition
Interleukin-1
Cell Survival
Estrogens
Cytoplasm
Machinery
Cell Proliferation
Adhesion
Cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Estrogen Receptor β Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis. / Han, Sang Jun; Jung, Sung Yun; Wu, San Pin; Hawkins, Shannon; Park, Mi Jin; Kyo, Satoru; Qin, Jun; Lydon, John P.; Tsai, Sophia Y.; Tsai, Ming Jer; Demayo, Francesco J.; O'Malley, Bert W.

In: Cell, Vol. 163, No. 4, 05.11.2015, p. 960-974.

Research output: Contribution to journalArticle

Han, SJ, Jung, SY, Wu, SP, Hawkins, S, Park, MJ, Kyo, S, Qin, J, Lydon, JP, Tsai, SY, Tsai, MJ, Demayo, FJ & O'Malley, BW 2015, 'Estrogen Receptor β Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis', Cell, vol. 163, no. 4, pp. 960-974. https://doi.org/10.1016/j.cell.2015.10.034
Han, Sang Jun ; Jung, Sung Yun ; Wu, San Pin ; Hawkins, Shannon ; Park, Mi Jin ; Kyo, Satoru ; Qin, Jun ; Lydon, John P. ; Tsai, Sophia Y. ; Tsai, Ming Jer ; Demayo, Francesco J. ; O'Malley, Bert W. / Estrogen Receptor β Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis. In: Cell. 2015 ; Vol. 163, No. 4. pp. 960-974.
@article{2a8902af589c4bbe80e0535cc65048ee,
title = "Estrogen Receptor β Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis",
abstract = "Summary Alterations in estrogen-mediated cellular signaling play an essential role in the pathogenesis of endometriosis. In addition to higher estrogen receptor (ER) β levels, enhanced ERβ activity was detected in endometriotic tissues, and the inhibition of enhanced ERβ activity by an ERβ-selective antagonist suppressed mouse ectopic lesion growth. Notably, gain of ERβ function stimulated the progression of endometriosis. As a mechanism to evade endogenous immune surveillance for cell survival, ERβ interacts with cellular apoptotic machinery in the cytoplasm to inhibit TNF-α-induced apoptosis. ERβ also interacts with components of the cytoplasmic inflammasome to increase interleukin-1β and thus enhance its cellular adhesion and proliferation properties. Furthermore, this gain of ERβ function enhances epithelial-mesenchymal transition signaling, thereby increasing the invasion activity of endometriotic tissues for establishment of ectopic lesions. Collectively, we reveal how endometrial tissue generated by retrograde menstruation can escape immune surveillance and develop into sustained ectopic lesions via gain of ERβ function.",
author = "Han, {Sang Jun} and Jung, {Sung Yun} and Wu, {San Pin} and Shannon Hawkins and Park, {Mi Jin} and Satoru Kyo and Jun Qin and Lydon, {John P.} and Tsai, {Sophia Y.} and Tsai, {Ming Jer} and Demayo, {Francesco J.} and O'Malley, {Bert W.}",
year = "2015",
month = "11",
day = "5",
doi = "10.1016/j.cell.2015.10.034",
language = "English (US)",
volume = "163",
pages = "960--974",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",

}

TY - JOUR

T1 - Estrogen Receptor β Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis

AU - Han, Sang Jun

AU - Jung, Sung Yun

AU - Wu, San Pin

AU - Hawkins, Shannon

AU - Park, Mi Jin

AU - Kyo, Satoru

AU - Qin, Jun

AU - Lydon, John P.

AU - Tsai, Sophia Y.

AU - Tsai, Ming Jer

AU - Demayo, Francesco J.

AU - O'Malley, Bert W.

PY - 2015/11/5

Y1 - 2015/11/5

N2 - Summary Alterations in estrogen-mediated cellular signaling play an essential role in the pathogenesis of endometriosis. In addition to higher estrogen receptor (ER) β levels, enhanced ERβ activity was detected in endometriotic tissues, and the inhibition of enhanced ERβ activity by an ERβ-selective antagonist suppressed mouse ectopic lesion growth. Notably, gain of ERβ function stimulated the progression of endometriosis. As a mechanism to evade endogenous immune surveillance for cell survival, ERβ interacts with cellular apoptotic machinery in the cytoplasm to inhibit TNF-α-induced apoptosis. ERβ also interacts with components of the cytoplasmic inflammasome to increase interleukin-1β and thus enhance its cellular adhesion and proliferation properties. Furthermore, this gain of ERβ function enhances epithelial-mesenchymal transition signaling, thereby increasing the invasion activity of endometriotic tissues for establishment of ectopic lesions. Collectively, we reveal how endometrial tissue generated by retrograde menstruation can escape immune surveillance and develop into sustained ectopic lesions via gain of ERβ function.

AB - Summary Alterations in estrogen-mediated cellular signaling play an essential role in the pathogenesis of endometriosis. In addition to higher estrogen receptor (ER) β levels, enhanced ERβ activity was detected in endometriotic tissues, and the inhibition of enhanced ERβ activity by an ERβ-selective antagonist suppressed mouse ectopic lesion growth. Notably, gain of ERβ function stimulated the progression of endometriosis. As a mechanism to evade endogenous immune surveillance for cell survival, ERβ interacts with cellular apoptotic machinery in the cytoplasm to inhibit TNF-α-induced apoptosis. ERβ also interacts with components of the cytoplasmic inflammasome to increase interleukin-1β and thus enhance its cellular adhesion and proliferation properties. Furthermore, this gain of ERβ function enhances epithelial-mesenchymal transition signaling, thereby increasing the invasion activity of endometriotic tissues for establishment of ectopic lesions. Collectively, we reveal how endometrial tissue generated by retrograde menstruation can escape immune surveillance and develop into sustained ectopic lesions via gain of ERβ function.

UR - http://www.scopus.com/inward/record.url?scp=84946209803&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84946209803&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2015.10.034

DO - 10.1016/j.cell.2015.10.034

M3 - Article

VL - 163

SP - 960

EP - 974

JO - Cell

JF - Cell

SN - 0092-8674

IS - 4

ER -