TWEAK/Fn14 promotes apoptosis of human endometrial cancer cells via caspase pathway.

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible immediate-early response protein 14 (Fn14) have been detected in several human tumors, and demonstrated to regulate multiple cellular responses, including proliferation, survival, migration, apoptosis and differentiation, suggesting roles in cancer. The objective of this study was to clarify the role of TWEAK/Fn14 in the development of human endometrial cancer. We found that TWEAK gene expression was down-regulated and Fn14 gene expression was up-regulated in human endometrial cancer specimens compared with that in normal endometrial specimens; TWEAK acting on Fn14 decreased cell viability by inducing apoptosis through caspase pathways in endometrial cancer cells. Our results suggest that Fn14 expression is high in endometrial cancers whereas local produced TWEAK may be low. TWEAK/Fn14 pathway activation may promote cancer cell apoptosis, which provides a new therapeutic target for human endometrial cancer treatment.