Integrin [beta]6 can be translationally regulated by eukaryotic initiation factor 4E: Contributing to colonic tumor malignancy

It is well known that both eukaryotic initiation factor 4E (eIF4E) and integrin [alpha]v[beta]6 can contribute to malignant behavior of colon cancer. We have found that integrin [alpha]v[beta]6 and eIF4E were co-expressed and positively correlated in colon cancer tissues. Recently, deregulation of the protein synthesis apparatus has begun to gain attention as a major participant in cancer development and progression. However, the regulation of integrin [beta]6 expression at translational level has never been investigated before. In present study, gene-silencing technique for eIF4E by small interfering RNA (siRNA) was used in all the subsequent experiments, in order to investigate whether eIF4E could translationally regulate expression of integrin [beta]6 in colon cancer SW480 and HT-29 cell lines. Additionally, the subsequent effects of eIF4E knockdown on cellular malignant behavior were observed. siRNA in SW480 and HT-29 transfectants. Subsequently, protein expression of [beta]6 was markedly suppressed, while mRNA expression of [beta]6 showed no significant variation before and after eIF4E RNA interfering. Therefore, it could be seen that eIF4E could upregulate the expression of [beta]6, without effect on [beta]6 mRNA expression. More importantly, after treated with eIF4E siRNA, cellular migratory capacity on fibronectin of HT-29 and [beta]6-transfected SW480 as well as their survival to 5-FU was decreased distinctly. Expression of integrin [beta]6 could be translationally regulated by eIF4E, which subsequently contributed to tumor malignancy through enhancing cellular migration, survival, anti-apoptosis, and chemoresistance of colon cancer in vitro. Thus, targeting eIF4E in integrin [alpha]v[beta]6 expressing tumors can be a potential therapeutic strategy for patients with colon cancer.