Cancer letters
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The poor prognosis of human ovarian cancer is partly due to its metastasis and recurrence. It has been demonstrated that tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK)-fibroblast growth factor inducible-14 (Fn14) signaling system may be a potential regulator of human tumorigenesis. The objective of this study was to understand the effect of TWEAK on ovarian cancer metastasis. ⋯ Blocking the NF-kappaB pathway with PDTC suppressed TWEAK-induced up-regulation of VEGF protein expression and cell metastasis. Our results suggest that TWEAK-Fn14 functions, in part, through the NF-kappaB signaling pathway to up-regulate VEGF expression to foster ovarian cancer cell metastasis. Targeted therapy against TWEAK-Fn14 signaling system as an adjuvant to surgery may improve clinical management of invasive ovarian cancer cells and advance the outcome of this devastating cancer.