Involvement of the Integrin α1β1 in the Progression of Colorectal Cancer.

Integrins are a family of heterodimeric glycoproteins involved in bidirectional cell signaling that participate in the regulation of cell shape, adhesion, migration, survival and proliferation. The integrin alpha 1 beta 1 is known to be involved in RAS/ERK proliferative pathway activation and plays an important role in fibroblast proliferation. In the small intestine, the integrin alpha 1 subunit is present in the crypt proliferative compartment and absent in the villus. We have recently shown that the integrin alpha 1 protein and transcript (ITGA1) are present in a large proportion of colorectal cancers (CRC) and that their expression is controlled by the MYC oncogenic factor. Considering that alpha 1 subunit/ITGA1 expression is correlated with MYC in more than 70% of colon adenocarcinomas, we postulated that the integrin alpha 1 beta 1 has a pro-tumoral contribution to CRC. In HT29, T84 and SW480 CRC cells, 1 subunit/ITGA1 knockdown resulted in a reduction of cell proliferation associated with an impaired resistance to anoikis and an altered cell migration in HT29 and T84 cells. Moreover, tumor development in xenografts was reduced in HT29 and T84 sh-ITGA1 cells, associated with extensive necrosis, a low mitotic index and a reduced number of blood vessels. Our results show that alpha 1 beta 1 is involved in tumor cell proliferation, survival and migration. This finding suggests that alpha 1 beta 1 contributes to CRC progression.