The MIG-2/integrin interaction strengthens cell-matrix adhesion and modulates cell motility.
Integrin-mediated cell-matrix adhesion plays an important role in control of cell behavior. We report here that MIG-2, a widely expressed focal adhesion protein, interacts with beta1 and beta3 integrin cytoplasmic domains. Integrin binding is mediated by a single site within the MIG-2 FERM domain. Functionally, the MIG-2/integrin interaction recruits MIG-2 to focal adhesions. Furthermore, using alphaIIbbeta3 integrin-expressing Chinese hamster ovary cells, a well described model system for integrin activation, we show that MIG-2 promotes integrin activation and enhances cell-extracellular matrix adhesion. Although MIG-2 is expressed in many cell types, it is deficient in certain colon cancer cells. Expression of MIG-2, but not of an integrin binding-defective MIG-2 mutant, in MIG-2-null colon cancer cells strengthened cell-matrix adhesion, promoted focal adhesion formation, and reduced cell motility. These results suggest that the MIG-2/integrin interaction is an important element in the cellular control of integrin-mediated cell-matrix adhesion and that loss of this interaction likely contributes to high motility of colon cancer cells.
Shi
Xiaohua
X
Department of Pathology, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
Ma
Yan-Qing
YQ
Tu
Yizeng
Y
Chen
Ka
K
Wu
Shan
S
Fukuda
Koichi
K
Qin
Jun
J
Plow
Edward F
EF
Wu
Chuanyue
C
D000818:Animals; D016466:CHO Cells; D018938:Caco-2 Cells; D002448:Cell Adhesion; D002465:Cell Movement / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006224:Cricetinae; D003412:Cricetulus; D005109:Extracellular Matrix / Q000378:metabolism*; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics
C477322:FERMT3 protein, human; D016023:Integrins; D008565:Membrane Proteins; D009363:Neoplasm Proteins