Pathogenic properties of human endometriotic epithelial cells require steroid receptor coactivator-2
Abstract
In brief: Although endometriosis is known to be a debilitating gynecological disease associated with chronic pelvic pain and infertility, our understanding of its molecular underpinnings is incomplete. Using experimentally induced nonhuman primate and murine endometriosis tissue along with a human ectopic endometriosis epithelial cell line, we reveal that steroid receptor coactivator-2 (and its downstream target S100A10) are important for the pathogenic properties of ectopic endometriotic epithelial cells, potentially providing new molecular vulnerabilities for future therapeutic invention.
Abstract: Commonly diagnosed in reproductive-age women, endometriosis is causally linked to subfertility, infertility, and chronic pelvic pain. Although theories exist on the etiopathogenesis of endometriosis, our understanding of its cellular and molecular underpinnings remain incomplete. We report that steroid receptor coactivator-2 (SRC-2), a member of the p160/SRC family of transcriptional coregulators, is expressed predominantly in epithelial cells of ectopic endometriotic lesions in the primate and mouse. Using an immortalized human endometriosis epithelial cell (iHEEC) line in conjunction with small interfering RNA–mediated silencing, we demonstrate that SRC-2 is essential for many of the pathogenic features ascribed to endometriotic lesion expansion, including sustained viability along with clonogenic, migratory, and invasive properties. Genome-scale iHEEC RNA-sequencing analysis implicates SRC-2 in a number of pathobiologies associated with the cellular phenotype of the ectopic endometriotic epithelial cell, including actin cytoskeleton reorganization. To underscore the utility of this RNA-sequencing dataset, we show that S100A10, a cytoarchitectural scaffolding protein, is responsive to SRC-2 and essential for many of the above cellular properties of the iHEEC that are ascribed to SRC-2. Because S100A10 dysregulation is strongly linked to the etiopathogenesis of a wide spectrum of malignancies, many of the molecular mechanisms that underlie S100A10’s role in cancer progression are predicted to be coopted in endometriosis. Therefore, these investigations highlight an unsuspected role for SRC-2 (and its transcriptome) in maintaining the pathogenetic phenotype of the ectopic endometriotic epithelial cell. Such findings support continued investigations of this coactivator and its downstream gene expression programs as potential targets for the prognosis, diagnosis, and/or treatment of this gynecological disorder in the future.
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BibTeX
@article{maurya2026pathogenic,
title = {{Pathogenic properties of human endometriotic epithelial cells require steroid receptor coactivator-2}},
author = {Vineet K Maurya and Sivagami Gunasekaran and Nisha Misra and David M Lonard and Pooja Popli and Ramakrishna Kommagani and Samantha Hrbek and Song Yong and Niraj Joshi and Asgerally T Fazleabas and John P Lydon},
journal = {Reproduction (Cambridge, England)},
year = {2026},
month = oct,
doi = {10.1093/reprod/xaag125},
url = {https://doi.org/10.1093/reprod/xaag125},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pathogenic properties of human endometriotic epithelial cells require steroid receptor coactivator-2
AU - Vineet K Maurya
AU - Sivagami Gunasekaran
AU - Nisha Misra
AU - David M Lonard
AU - Pooja Popli
AU - Ramakrishna Kommagani
AU - Samantha Hrbek
AU - Song Yong
AU - Niraj Joshi
AU - Asgerally T Fazleabas
AU - John P Lydon
PY - 2026
DA - 2026/10/06
JO - Reproduction (Cambridge, England)
DO - 10.1093/reprod/xaag125
UR - https://doi.org/10.1093/reprod/xaag125
AB - In brief: Although endometriosis is known to be a debilitating gynecological disease associated with chronic pelvic pain and infertility, our understanding of its molecular underpinnings is incomplete. Using experimentally induced nonhuman primate and murine endometriosis tissue along with a human ectopic endometriosis epithelial cell line, we reveal that steroid receptor coactivator-2 (and its downstream target S100A10) are important for the pathogenic properties of ectopic endometriotic epithelial cells, potentially providing new molecular vulnerabilities for future therapeutic invention. Abstract: Commonly diagnosed in reproductive-age women, endometriosis is causally linked to subfertility, infertility, and chronic pelvic pain. Although theories exist on the etiopathogenesis of endometriosis, our understanding of its cellular and molecular underpinnings remain incomplete. We report that steroid receptor coactivator-2 (SRC-2), a member of the p160/SRC family of transcriptional coregulators, is expressed predominantly in epithelial cells of ectopic endometriotic lesions in the primate and mouse. Using an immortalized human endometriosis epithelial cell (iHEEC) line in conjunction with small interfering RNA–mediated silencing, we demonstrate that SRC-2 is essential for many of the pathogenic features ascribed to endometriotic lesion expansion, including sustained viability along with clonogenic, migratory, and invasive properties. Genome-scale iHEEC RNA-sequencing analysis implicates SRC-2 in a number of pathobiologies associated with the cellular phenotype of the ectopic endometriotic epithelial cell, including actin cytoskeleton reorganization. To underscore the utility of this RNA-sequencing dataset, we show that S100A10, a cytoarchitectural scaffolding protein, is responsive to SRC-2 and essential for many of the above cellular properties of the iHEEC that are ascribed to SRC-2. Because S100A10 dysregulation is strongly linked to the etiopathogenesis of a wide spectrum of malignancies, many of the molecular mechanisms that underlie S100A10’s role in cancer progression are predicted to be coopted in endometriosis. Therefore, these investigations highlight an unsuspected role for SRC-2 (and its transcriptome) in maintaining the pathogenetic phenotype of the ectopic endometriotic epithelial cell. Such findings support continued investigations of this coactivator and its downstream gene expression programs as potential targets for the prognosis, diagnosis, and/or treatment of this gynecological disorder in the future.
SN - 1470-1626
SN - 1741-7899
ER -