Integrin β1 mediates 5-fluorouracil chemoresistance under translational control of eIF4E in colorectal cancer.

PURPOSE: In recent years, aberrant mRNA translational control has gained much attention as a critical player in the malignant process of tumors. Eukaryotic initiation factor 4E (eIF4E), by binding to the mRNA cap, can regulate specific protein synthesis, contributing to malignancy in human tumors. However, integrin β1 mediated chemoresistance under translational control remains unknown in colorectal cancer. PATIENTS AND METHODS: The expression relationship between eIF4E and Integrin β1, along with their clinical significance was investigated in colorectal cancerous tissues of 118 cases using immunohistochemistry. Cell transfection techniques of small interfering RNA (siRNA) and cDNA expression plasmid were applied to investigate the molecular relationship of integrin β1 and eIF4E and their biological effects on 5FU resistance in SW480 and LoVo cell lines. RESULTS: The expression of eIF4E and integrin β1 was positively correlated in colorectal cancer, and patients with high expressions of both markers tended to have a worse prognosis according to a Kaplan-Meier survival analysis. Integrin β1 could contribute to 5-fluorouracil (5FU) resistance in colorectal cancer cell lines. Moreover, the protein expression of β1 could be regulated by eIF4E, interestingly, without any change of mRNA expression level. Significantly, Hoechst/PI double staining and an MTT assay proved integrin β1 could contribute to cellular survival and 5FU resistance under translational control of eIF4E in these cells. CONCLUSION: We conclude that integrin β1 mediated 5FU chemo resistance in colorectal cancer could be translationally regulated by eIF4E. Promisingly, targeting key molecules of this translational apparatus may provide an innovative therapeutic strategy for colorectal cancer.