Integrin αvβ6 Contributes To The Malignancy Of Colon Cancer Under The Translational Control Of EIF4E

Part Ⅰ Protein expression of eIF4E and Integrin αvβ6 in colon cancer can predict clinical significance and reveal their correlationBackgroundBoth eukaryotic translation initiation factor 4E (eIF4E) and integrin αvβ6 play an important role in the development and progression of cancer. The aim of this study was to investigate the expression of eIF4E and integrin αvβ6, their clinical significance as well as the two proteins’correlation in colonic carcinoma tissues.MethodsThe expression levels of eIF4E and integrin αvβ6 were analyzed in colon cancerous and paraneoplastic tissues of 138 cases via tissue microarray (TMA)-immunohistochemistry. And their clinical significance as well as the two proteins’correlation was also investigated.ResultsThe protein expressions of integrin αvβ6 and elF4E in colonic cancer tissue were significantly higher than that in normal colonic tissue (P<0.05). The expression of eIF4E was significantly associated with clinical TNM stage (P=0.009), while T stage (P=0.011), M stage (P=0.034) and TNM stage(P= 0.012) were significantly associated with integrin αvβ6 expression. Moderately weak correlation existed between the two proteins (r=0.299, P<0.001).ConclusionThe expressions of eIF4E and integrin αvβ6 were closely related to clinicalpathological features of patients with colon cancer. Also, there was a certain correlation between the two proteins’expression in colon cancer tissues. And the potential signaling loop involving them may provide a helpful therapeutic target in prevention and treatment of colon cancer. (P=0.011), M stage (P=0.034) and TNM stage(P= 0.012) were significantly associated with integrin αvβ6 expression. Moderately weak correlation existed between the two proteins (r=0.299, P<0.001).ConclusionThe expressions of eIF4E and integrin αvβ6 were closely related to clinicalpathological features of patients with colon cancer. Also, there was a certain correlation between the two proteins’expression in colon cancer tissues. And the potential signaling loop involving them may provide a helpful therapeutic target in prevention and treatment of colon cancer.Part Ⅱ ElF4E can translationally regulate Integrin αvβ6 expression contributing to the malignancy of colon cancerBackgroundIt is well known that both eukaryotic initiation factor 4E (eIF4E) and integrin αvβ6 can contribute to malignant behaviors of colon cancer. Recently, deregulation of the protein synthesis apparatus has begun to gain attention as a major player in cancer development and progression. However, the regulation of integrin β6 expression at translational level has never been investigated before.MethodsIn present study, gene silencing technique for eIF4E by small interfering RNA (siRNA) was used in all the following experiments, in order to investigate whether eIF4E could translationally regulate expression of integrin β6 in colon cancer SW480 and HT-29 cell lines. Furthermore, the subsequent effects of eIF4E knockdown on cellular malignant behavior were observed.ResultsWe examined expression of eIF4E was reduced to a low level after treatment of eIF4E siRNA in SW480 and HT-29 transfectants. Subsequently, protein expression of β6 was markedly suppressed, while mRNA expression of β6 showed no significant variation before and after eIF4E RNA interfering. More importantly, after treated with eIF4E siRNA, cellular migratory capacity on fibronectin of HT29 and (36-transfected SW480 as well as their survival to 5-FU was decreased distinctly.ConclusionExpression of integrin β6 could be translationally regulated by eIF4E, which subsequently contributed to tumor malignancy through enhancing cellular migration, survival, anti-apoptosis and chemo resistance of colon cancer. Therefore, targeting eIF4E in integrin αvβ6 expressing tumors might be a potential therapeutic strategy for patients with colon cancer.