Early Growth Response 1 Transcription Factor Is Essential for the Pathogenic Properties of Human Endometriotic Epithelial Cells

Authors

Vineet K Maurya
Maria M Szwarc
Rodrigo Fernandez-Valdivia
David M Lonard
Song Yong
Niraj Joshi
Asgerally T Fazleabas
John P Lydon

Publication Date

8-1-2022

Journal

Reproduction

DOI

10.1530/REP-22-0123

PMID

35679138

PMCID

PMC9339520

PubMedCentral® Posted Date

8-1-2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Cell Movement, Early Growth Response Protein 1, Endometriosis, Endometrium, Epithelial Cells, Female, Humans, Stromal Cells, Transcription Factors

Abstract

Although a non-malignant gynecological disorder, endometriosis displays some pathogenic features of malignancy, such as cell proliferation, migration, invasion and adaptation to hypoxia. Current treatments of endometriosis include pharmacotherapy and/or surgery, which are of limited efficacy and often associated with adverse side effects. Therefore, to develop more effective therapies to treat this disease, a broader understanding of the underlying molecular mechanisms that underpin endometriosis needs to be attained. Using immortalized human endometriotic epithelial and stromal cell lines, we demonstrate that the early growth response 1 (EGR1) transcription factor is essential for cell proliferation, migration and invasion, which represent some of the pathogenic properties of endometriotic cells. Genome-wide transcriptomics identified an EGR1-dependent transcriptome in human endometriotic epithelial cells that potentially encodes a diverse spectrum of proteins that are known to be involved in tissue pathologies. To underscore the utility of this transcriptomic data set, we demonstrate that carbonic anhydrase 9 (CA9), a homeostatic regulator of intracellular pH, is not only a molecular target of EGR1 but is also important for maintaining many of the cellular properties of human endometriotic epithelial cells that are also ascribed to EGR1. Considering therapeutic intervention strategies are actively being developed for EGR1 and CAIX in the treatment of other pathologies, we believe EGR1 and its transcriptome (which includes CA9) will offer not only a new conceptual framework to advance our understanding of endometriosis but will also furnish new molecular vulnerabilities to be leveraged as potential therapeutic options in the future treatment of endometriosis.

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