PKC promotes the migration of colon cancer cells by regulating the internalization and recycling of integrin αvβ6

Recently published studies have suggested that integrin trafficking is necessary to support cell migration, but the role of internalization and recycling of integrin alpha v beta 6 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 beta 6 cytoplasmic domain could interrupt the internalization of integrin alpha v beta 6, but had no effect on its recycling. Furthermore, integrin alpha v beta 6 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 alpha v beta 6, which could facilitate rapid redistribution of integrin alpha v beta 6 and increase cell motility. When colon cancer cells became crowded, the increase in alpha v beta 6 levels at the cell surface was not accompanied by a change in total alpha v beta 6 expression in cell lysates. This change may be due to a redistribution of alpha v beta 6 in cell microstructures and a rapid cellular response towards the demands of migration. Crown Copyright (C) 2011 Published by Elsevier Ireland Ltd. All rights reserved.