title: PKC promotes the migration of colon cancer cells by regulating the internalization and recycling of integrin αvβ6.
abstract: 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.
authors: Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, Shandong, PR China.
authors: Jian
authors: J
authors: Wang
authors: Jingjing
authors: J
authors: Wu
authors: Jianguo
authors: J
authors: Hong
authors: Rong
authors: R
authors: Chen
authors: Kesen
authors: K
authors: Xu
authors: Weibo
authors: W
authors: Niu
authors: Cheng
authors: C
authors: Peng
authors: Enyu
authors: E
authors: Liu
authors: Jiayong
authors: J
authors: Wang
authors: Song
authors: S
authors: Liu
authors: Michael
authors: M
authors: Agrez
authors: Jun
authors: J
authors: Niu
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D003110:Colonic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D003593:Cytoplasm / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D000951:Antigens, Neoplasm; D005419:Flavonoids; D016023:Integrins; C073878:integrin alphavbeta6; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one