FKBP38 expression level dictates paclitaxel resistance via interacting with Bcl-2 in endometrial cancer.

Endometrial cancer (EC) is a gynecological malignancy that faces the serious challenge of chemotherapy resistance. Therefore, there is an urgent clinical need to investigate this issue. In this study, we focused on the potential role of FKBP38, a membrane-bound chaperone protein primarily located in the outer mitochondrial membrane. Previous studies have reported reduced FKBP38 expression in ovarian and breast cancer tissues. In this study, we found that FKBP38 expression was significantly decreased in human EC tissues and correlated with poor overall survival in patients receiving chemotherapy. Knockdown of FKBP38 expression in EC cells increased the half-maximal inhibitory concentration of paclitaxel and attenuated the therapeutic response in xenograft models. FKBP38 co-localized and interacted with Bcl-2, and reduced FKBP38 expression inhibited paclitaxel-induced apoptosis by stabilizing mitochondrial function. Importantly, under paclitaxel treatment, FKBP38 knockdown not only increased Bcl-2 expression but also prevented the binding of Bcl-2 to the pro-apoptotic protein, Bad. Collectively, these findings imply that FKBP38 inhibits paclitaxel resistance by interacting with Bcl-2, thereby preserving mitochondrial function. Thus, FKBP38 may serve as a suitable biomarker for targeted antimetabolite therapy in EC.