Fibronectin promotes cell proliferation and invasion through mTOR signaling pathway activation in gallbladder cancer

摘要: Fibronectin (FN), a heterodimeric glycoprotein overexpressed in several types of tumors, has been implicated cancer progression via the activation integrin-mediated pro-oncogenic pathways. The FN level human bile fluid is dramatically increased malignant biliary diseases; however, expression and its biological functions gallbladder (GBC) remain unknown. In this study, we found that was GBC tissues associated with worse prognosis patients. vitro experimental studies indicated exogenous significantly enhanced cell proliferation, invasion active MMP-9 secretion lines (GBC-SD NOZ). Moreover, key kinases mTOR signaling pathway, including FAK, Akt, 4E-BP1, were markedly activated time-dependent manner FN-treated GBC-SD NOZ cells. IHC statistical analyses validated positively correlated phosphorylation levels 4E-BP1 protein tissues. Furthermore, rapamycin, specific inhibitor mTOR, almost completely blocked FN-induced also partially abrogated stimulatory effects on proliferation invasion. vivo, treatment promoted metastasis cells Akt/mTOR/4E-BP1 cascade. These findings demonstrate may play critical role modulation pathway during progression.