Integrin β6 can be translationally regulated by eukaryotic initiation factor 4E: Contributing to colonic tumor malignancy

• Published in: Tumor biology Vol. 36; no. 8; pp. 6541 - 6550
• Main Authors: Enyu, Liu, Zhengchuan, Niu, Jiayong, Wang, Benjia, Liang, Qi, Sun, Ruixi, Qin, Cheng, Peng, Khan, Abdul Qadir, Wei, Song, Jun, Niu
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.08.2015
• Subjects: Antigens, Neoplasm - biosynthesis; Antigens, Neoplasm - genetics; Apoptosis - genetics; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Proliferation - genetics; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Eukaryotic Initiation Factor-4E - antagonists & inhibitors; Eukaryotic Initiation Factor-4E - biosynthesis; Eukaryotic Initiation Factor-4E - genetics; Gene Expression Regulation, Neoplastic; HT29 Cells; Humans; Integrins - biosynthesis; Integrins - genetics; Research Article; RNA, Messenger - biosynthesis; eIF4E; Protein synthesis; Integrin β6; Translation initiation
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-015-3348-8

It is well known that both eukaryotic initiation factor 4E (eIF4E) and integrin αvβ6 can contribute to malignant behavior of colon cancer. We have found that integrin αvβ6 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 β6 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 β6 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 β6 was markedly suppressed, while mRNA expression of β6 showed no significant variation before and after eIF4E RNA interfering. Therefore, it could be seen that eIF4E could upregulate the expression of β6, without effect on β6 mRNA expression. More importantly, after treated with eIF4E siRNA, cellular migratory capacity on fibronectin of HT-29 and β6-transfected SW480 as well as their survival to 5-FU was decreased distinctly. Expression of integrin β6 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 αvβ6 expressing tumors can be a potential therapeutic strategy for patients with colon cancer.