PKC promotes the migration of colon cancer cells by regulating the internalization and recycling of integrin alphavbeta6.

摘要

Recently published studies have suggested that integrin trafficking is necessary to support cell migration, but the role of internalization and recycling of integrin alphavbeta6 in colon cancer cells remained unclear. In our study, we demonstrated the existence of the integrin cycle and found that inhibition of ERK2 phosphorylation by PD98059 or deletion of the ERK2 direct binding site on the beta6 cytoplasmic domain could interrupt the internalization of integrin alphavbeta6, but had no effect on its recycling. Furthermore, integrin alphavbeta6 trafficking played a key role in the migration of colon cancer cells towards fibronectin. Activation of PKC significantly accelerated the internalization and recycling of integrin alphavbeta6, which could facilitate rapid redistribution of integrin alphavbeta6 and increase cell motility. When colon cancer cells became crowded, the increase in alphavbeta6 levels at the cell surface was not accompanied by a change in total alphavbeta6 expression in cell lysates. This change may be due to a redistribution of alphavbeta6 in cell microstructures and a rapid cellular response towards the demands of migration.