PARP-1 couples β-catenin/TCF4 signaling to epithelial-mesenchymal transition in endometriosis

Endometriosis exhibits epithelial–mesenchymal transition (EMT)-aligned traits that promote invasion and lesion persistence. We investigated whether poly(ADP-ribose) polymerase-1 (PARP-1) coordinates β-catenin/TCF4 activity with EMT programs and whether these features are amenable to pharmacologic inhibition. PARP-1 and EMT markers were profiled in normal endometrium and ovarian endometriotic lesions. In endometriotic epithelial cells, PARP-1 levels were modulated by overexpression or siRNA and effects on EMT markers and motility were quantified. Association of PARP-1 with β-catenin/TCF4 complexes was evaluated, and a lesion model was used to test the impact of PARP inhibition on EMT features and lesion burden. PARP-1 was elevated in ectopic lesions and aligned with EMT-associated marker shifts. PARP-1 gain increased β-catenin/TCF4 activity, remodeled EMT markers, and enhanced motility, whereas PARP-1 loss produced the opposite pattern. Analyses supported PARP-1 association with β-catenin/TCF4 complexes. Pharmacologic PARP inhibition attenuated β-catenin/TCF4-aligned EMT features in vitro and reduced lesion growth with concurrent marker normalization in vivo. These findings indicate that PARP-1 couples Wnt/β-catenin signaling to EMT programs in endometriosis and identify PARP inhibition as a tractable approach to modulate these phenotypes.

Endometriosis; Epithelial–mesenchymal transition; PARP inhibitor; Poly(ADP-ribose) polymerase 1; T-cell factor 4; β-catenin.