The β6-integrin-ERK/MAP kinase pathway contributes to chemo resistance in colon cancer.

5-Fluorouracil (5-FU) is the most widely used chemo drug for the treatment of colon cancer. However, a sub-population of colon cancer patients do not respond to 5-FU and this treatment does not provide survival benefit due to chemo resistance. The mechanisms involved in 5-FU resistance are not fully understood and multiple factors have been involved in the sensitivity of cancer cells to 5-FU. We previously reported that β6-integrin plays an important role in invasion, metastasis and degradation of extracellular matrix of colon cancer. In this study, we investigated whether β6-integrin is associated with chemo resistance in colon cancer. We found that over-expression of β6-integrin protected SW480 and HT-29 colon cancer cells from 5-FU-induced growth inhibition and apoptosis, which were accompanied by changes in cytochrome C released from the mitochondria and activity of caspase-3 and caspase-9. Moreover, β6-integrin resulted in up-regulation of Bcl-2 and down-regulation of Bax. We also found that β6-integrin induced 5-FU resistance through the ERK/MAP kinase pathway and the β6-ERK2 direct binding. The results indicate β6-integrin might be a novel therapeutic target in colon cancer therapy.