Mechanism of FOXC1 in the invasion and migration of ectopic endometrial stromal cells in endometriosis

Endometriosis (EM) is a common and challenging condition of reproductive-aged women and its pathogenesis is associated with endometrial stromal cells (ESCs). This study aimed to explore the role of FOXC1 in invasion and migration of ectopic ESCs (Ect-ESCs) in EM. Human eutopic and Ect-ESCs were isolated and identified, followed by detection of the levels of FOXC1, IGF2BP3, and m6A in ITGB1 in eutopic and Ect-ESCs. After interfering with FOXC1 in Ect-ESCs, cell invasion and migration were assessed. RNA immunoprecipitation assay was conducted to investigate the enrichment of IGF2BP3 or m6A on ITGB1. ITGB1 mRNA stability was examined. The roles of IGF2BP3 or ITGB1 in the invasion and migration of Ect-ESCs were verified by combined experiments. We found that FOXC1, IGF2BP3, and ITGB1 were upregulated in Ect-ESCs. FOXC1 downregulation inhibited invasion and migration of Ect-ESCs. Mechanically, FOXC1 bound to the IGF2BP3 promoter to positively regulate IGF2BP3 expression, promoted ITGB1 mRNA stability in an m6A-dependent manner, and increased ITGB1 transcription. Overexpression of IGF2BP3 or ITGB1 attenuated the inhibitory role of FOXC1 downregulation in invasion and migration of Ect-ESCs. In conclusion, FOXC1 promoted IGF2BP3 expression and stabilized ITGB1 mRNA in an m6A-dependent manner, thus promoting invasion and migration of Ect-ESCs. Similar content being viewed by others Data availability The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request. Abbreviations - EM: - Endometriosis - ESCs: - endometrial stromal cells - FOXC1: - forkhead box C1 - Ect-ESCs: - ectopic ESCs - FOX: - Forkhead box - m6A: - N6-methyladenosine - IGF2BPs: - Insulin-like growth factor 3 mRNA binding proteins - ITG: - Integrins - ITGB1: - ITG Integrins β 1 - DMEM: - Dulbecco’s modified Eagle medium - FBS: - fetal bovine serum - PBS: - phosphate buffer solution - IgG: - immunoglobulin G - DAB: - diaminobenzidine - siRNAs: - Small interfering RNAs - ChIP: - Chromatin immunoprecipitation - SDS: - sodium dodecyl sulfate - WT: - wild-type - MUT: - mutant - PCR: - polymerase chain reaction - RT-qPCR: - real-time quantitative PCR - cDNA: - complementary DNA - GAPDH: - glyceraldehyde-3-phosphate dehydrogenase - SDS-PAGE: - sodium dodecyl sulfate polyacrylamide gel electrophoresis - ANOVA: - analysis of variance

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We acknowledge investigators and participants in the study. Funding This study was not funded. Author information Authors and Affiliations Contributions RH designed the study and drafted the manuscript. YL and YZ performed experiments. YL revised the manuscript. All authors read and approved of the final manuscript. Corresponding author Ethics declarations Competing interests The authors declare no competing interests. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Huang, R., Li, Y. & Zhang, Y. Mechanism of FOXC1 in the invasion and migration of ectopic endometrial stromal cells in endometriosis. Pflugers Arch - Eur J Physiol 478, 9 (2026). https://doi.org/10.1007/s00424-025-03137-w Received: Revised: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s00424-025-03137-w