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 αvβ6 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 β6 cytoplasmic domain could interrupt the internalization of integrin αvβ6, but had no effect on its recycling. Furthermore, integrin αvβ6 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 αvβ6, which could facilitate rapid redistribution of integrin αvβ6 and increase cell motility. When colon cancer cells became crowded, the increase in αvβ6 levels at the cell surface was not accompanied by a change in total αvβ6 expression in cell lysates. This change may be due to a redistribution of αvβ6 in cell microstructures and a rapid cellular response towards the demands of migration.

► Internalization and recycling of integrin αvβ6 are detected in colon cancer cells.
► β6-ERK2 binding contributes to the internalization but not the recycling of αvβ6.
► αvβ6 trafficking plays a key role in the migration of colon cancer cells.
► PKC activation accelerates αvβ6 trafficking and increases cell motility.
► Upregulation of cell surface αvβ6 with cell crowding is due to αvβ6 redistribution.