Dual targeting of CXCR4 and EZH2 in endometriosis

Sarah Brunty, Kassey Wagner, Taylor Fleshman, Morgan Ruley, Brenda Mitchell, Nalini Santanam
iScience · 2025 · vol. 28(4) , pp. 112143 · doi:10.1016/j.isci.2025.112143 · PMID:40171488 · W4408073196
article OA: gold CC0
🔓 Open OA copy View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

Endometriotic peritoneal fluid increased CXCR4, EZH2, and H3K27me3 expression, with dual inhibition of CXCR4 and EZH2 reducing cell proliferation and migration in human endometrial stromal cells.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

We recently showed that endometriotic peritoneal fluid (PF) altered the regulation of enhancer of zeste homolog 2 (EZH2) and H3K27me3. This study aimed to determine if PF by regulating EZH2/H3K27me3 modulated C-X-C chemokine receptor type 4 (CXCR4), a major chemokine involved in the proliferation and migration processes in endometriosis. Endometriotic PF induced the mRNA expression of CXCR4 and EZH2 and protein expression of H3K27me3 in human endometrial stromal cells (hESCs) and eutopic endometrium (Eu). CXCR4 inhibitor, AMD3100, decreased the PF-induced expression of these factors and reduced migration, but increased the proliferation of hESCs. In contrast, the EZH2 inhibitor, GSK126, decreased the expression of EZH2 and H3K27me3 and reduced proliferation, but increased the expression of CXCR4 and migration of hESCs. A combination of both inhibitors decreased the expression of CXCR4, EZH2, and H3K27me3, as well as reduced cell proliferation and migration. Our study suggests that targeting both CXCR4 (inflammation) and EZH2 (epigenetics) may be a better alternative for women with endometriosis.

My notes (saved in your browser only)

Condition tags

endometriosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (64)

Source provenance

europepmc
last seen: 2026-06-04T01:30:01.192114+00:00
openalex
last seen: 2026-06-04T00:00:01.174412+00:00
pmc
last seen: 2026-05-13T20:22:03.195721+00:00
pubmed
last seen: 2026-05-29T00:31:35.037505+00:00
License: CC0 · commercial use OK