P-cadherin cooperates with insulin-like growth factor-1 receptor to promote metastatic signaling of gonadotropin-releasing hormone in ovarian cancer via p120 catenin.

摘要: Gonadotropin-releasing hormone (GnRH) is a potent prometastatic factor in ovarian cancer, but the intracellular signaling events are not well understood. The classical Gα(q)-phospholipase C signal transduction pathway known to operate pituitary involved GnRH actions at non-pituitary targets. Here we showed that treatment of cancer cells led rapid and remarkable tyrosine phosphorylation p120 catenin (p120(ctn)), which was mediated by P-cadherin. use P-cadherin small interfering RNA or neutralizing antibodies inhibit expression function resulted diminished p120(ctn) activation, confirming effect specific. On exploring how P-cadherin, lacks intrinsic kinase activity, might regulate activation p120(ctn), found could induce ligand-independent insulin-like growth factor-1 receptor (IGF-1R). Inhibition IGF-1R its activity significantly inhibited GnRH-induced subsequent cell migration invasion. In addition, regulation associated with complex formation between this also observed be vivo correlated metastasis. Furthermore, using mouse model metastasis, knockdown shown diminish peritoneal dissemination tumors ascites formation. These findings suggest for first time can initiate an outside-in through cross-talk IGF-1R, thus providing novel molecular mechanism may control high level aggressiveness invasion metastasis potential characteristic cancer.