CRIF1 promotes aggressive phenotypes and is associated with reduced paclitaxel-induced apoptosis in endometrial cancer cells through Wnt/β-catenin-related signaling

Endometrial cancer (EC) is a common gynecological malignancy, and chemoresistance remains a major challenge in advanced-stage diseases. CR6-interacting factor 1 (CRIF1) has been implicated in cancer progression; however, its role in EC and paclitaxel response is unclear. CRIF1 expression was examined in 95 EC tissues and matched adjacent normal tissues by immunohistochemistry, RT-qPCR, and western blotting, and its clinicopathological associations were assessed. CRIF1 overexpression was evaluated in Ishikawa cells using proliferation, migration, apoptosis, reactive oxygen species, and glycolysis assays. Wnt/β-catenin-associated signaling was investigated using Wnt-C59. CRIF1 was upregulated in EC tissues, and higher expression was associated with advanced FIGO stage, higher histological grade, deeper myometrial invasion, and increased Ki-67 positivity. Under chemotherapy-free baseline conditions, CRIF1 overexpression increased the proliferation and migration of Ishikawa cells. Following paclitaxel treatment, CRIF1 overexpression was associated with reduced apoptosis, lower oxidative stress, enhanced glycolytic activity and increased Wnt/β-catenin-related signaling. Wnt-C59 partially attenuated these effects, supporting the potential contribution of Wnt/β-catenin-associated signaling. These findings suggest that CRIF1 may have context-dependent effects in EC and may be associated with cellular adaptation to paclitaxel-induced stress. Whether CRIF1 influences responses to other chemotherapeutic agents or contributes to clinically relevant paclitaxel resistance remains to be determined.