The alpha v beta 6 integrin promotes proliferation of colon carcinoma cells through a unique region of the beta 6 cytoplasmic domain.
Cell-matrix interactions are assumed to be important in regulating differentiation and tumor cell growth; however, the precise roles of individual matrix receptors in producing cellular responses are still unclear. We have previously described the alpha v beta 6 integrin, an epithelial cell fibronectin receptor expressed in many carcinoma cell lines. Here we show that heterologous expression of alpha v beta 6 in a human colon carcinoma cell line (SW480) enhances the proliferative capacity of these cells, both in vitro and in vivo in nude mice. This property of alpha v beta 6 correlates with the presence of an 11-amino acid region at the COOH terminus of the beta 6 cytoplasmic domain. This 11-amino acid sequence is required for the growth stimulatory effect, but not for other functions of the beta 6 cytoplasmic domain, such as promoting cell adhesion and focal contact localization.
Agrez
M
M
Department of Medicine, University of California, San Francisco.
Chen
A
A
Cone
R I
RI
Pytela
R
R
Sheppard
D
D
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm; D002448:Cell Adhesion; D002455:Cell Division; D002460:Cell Line; D003094:Collagen; D003110:Colonic Neoplasms / Q000473:pathology*; D005353:Fibronectins; D006801:Humans; D016023:Integrins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D017469:Receptors, Fibronectin / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D005353:Fibronectins; D016023:Integrins; D017469:Receptors, Fibronectin; C073878:integrin alphavbeta6; D003094:Collagen