| First Author | Mizutani K | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 42 | Pages | 36667-76 |
| PubMed ID | 21880726 | Mgi Jnum | J:183192 |
| Mgi Id | MGI:5317999 | Doi | 10.1074/jbc.M110.200535 |
| Citation | Mizutani K, et al. (2011) Interaction of nectin-like molecule 2 with integrin alpha6beta4 and inhibition of disassembly of integrin alpha6beta4 from hemidesmosomes. J Biol Chem 286(42):36667-76 |
| abstractText | In normal epithelial cells, integrin alpha(6)beta(4) is abundantly expressed and forms hemidesmosomes, which is a cellular structure that mediates cell-extracellular matrix binding. In many types of cancer cells, integrin alpha(6)beta(4) is up-regulated, laminin is cleaved, and hemidesmosomes are disrupted, eventually causing an enhancement of cancer cell movement and facilitation of their invasion. We previously showed that the immunoglobulin-like cell adhesion molecule Necl-2 (Nectin-like molecule 2), known as a tumor suppressor, inhibits cancer cell movement by suppressing the ErbB3/ErbB2 signaling. We show here that Necl-2 interacts in cis with integrin alpha(6)beta(4). The binding of Necl-2 with integrin beta(4) was mediated by its extracellular region. In human colorectal adenocarcinoma Caco-2 cells, integrin alpha(6)beta(4) was localized at hemidesmosomes. Small interfering RNA-mediated suppression of Necl-2 expression enhanced the phorbol ester-induced disruption of the integrin alpha(6)beta(4) complex at hemidesmosomes, whereas expression of Necl-2 suppressed the disruption of this structure. These results indicate that tumor-suppressive functions of Necl-2 are mediated by the stabilization of the hemidesmosome structure in addition to the inhibition of the ErbB3/ErbB2 signaling. |
