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| Src-induced de-regulation of E-cadherin in colon cancer cells requires integrin signalling |
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| Author(s): Avizienyte E, Wyke AW, Jones RJ, McLean GW, Westhoff MA, Brunton VG, Frame MC |
| Source: NATURE CELL BIOLOGY Volume: 4 Issue: 8 Pages: 632-638 Published: AUG 2002 |
| Times Cited: 141 References: 24 |
| Abstract: Although Src expression and activity are often elevated in colon cancer(1-3), the precise consequences of overexpression of the non-catalytic Src homology (SH) domains, or enhanced catalytic activity, are unknown. We show that, in KM12C colon cancer cells, elevated Src activity causes the components of adherens junctions, including vinculin, to be redistributed to Src-induced integrin-adhesion complexes. Specifically, elevated Src activity blocks proper assembly of cell-cell contacts after cells are switched from media containing a low level of calcium to media containing a high level of calcium, and E-cadherin remains internalized. In contrast, although elevated expression of the non-catalytic domains of Src is sufficient to induce assembly of integrin-adhesion complexes, it does not induce disorganization of E-cadherin-associated intercellular contacts. Surprisingly, Src-induced disruption of E-cadherin localization requires specific integrin signalling, because E-cadherin redistribution is blocked by loss of cell-matrix interaction, or by inhibitory antibodies to alpha(v) or beta(1) integrin subunits. Furthermore, phosphorylation of the integrin-regulated focal adhesion kinase (FAK) on Src-specific sites is required for Src-induced de-regulation of E-cadherin, demonstrating interdependence between integrin-induced signals and cadherin-associated adhesion changes induced by Src. |
| Document Type: Article |
| Language: English |
| Reprint Address: Frame, MC (reprint author), Western Infirm & Associated Hosp, Beatson Oncol Ctr, Glasgow G11 6NT, Lanark Scotland |
Addresses:
1. Univ Glasgow, Inst Biol & Life Sci, Glasgow G12 8QQ, Lanark Scotland
2. Beatson Inst Canc Res, Canc Res UK Beatson Labs, Glasgow G61 1BD, Lanark Scotland |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Cell Biology |
| IDS Number: 579WK |
| ISSN: 1465-7392 |
| DOI: 10.1038/ncb829 |
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