Figure 1. SRC1 fragments on the endometriotic pathway. According to a study in Nature Medicine, inhibition of a pathway that produces a fragment of nuclear receptor coactivator 1 (NCOA1; SRC1) in endometrial (uterine lining) cells could help treat endometriosis.

During menstruation, cells shed from the endometrium [a] can respond to local increases in tumor necrosis factor-a (TNF-a) [b] by upregulating matrix metalloproteinase 9 (MMP9) [c], which cleaves a 70 kDa, C-terminal fragment from full-length (160 kDa) SRC1 [d]. In turn, the fragment prevents TNF-a-induced activation of procaspase-8 to caspase-8 (CASP8; FLICE) [e(1)] and consequent apoptotic sig­naling, and it promotes the epithelial-mesenchymal transition (EMT) [e(2)] by an unknown mechanism, thereby inducing antiapoptotic and invasive phenotypes, respectively. These characteristics are the hallmarks of endometriotic cells [f] and enable them to form endometriotic lesions [g] on the ovaries and/or elsewhere in the peritoneum.