Interaction of nectin-like molecule 2 with integrin alpha6beta4 and inhibition of disassembly of integrin alpha6beta4 from hemidesmosomes |
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Authors: | Mizutani Kiyohito Kawano Satoshi Minami Akihiro Waseda Masazumi Ikeda Wataru Takai Yoshimi |
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Affiliation: | Division of Molecular and Cellular Biology, Department of Biochemistry, and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Hyogo, Japan. |
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Abstract: | In normal epithelial cells, integrin α(6)β(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 α(6)β(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 α(6)β(4). The binding of Necl-2 with integrin β(4) was mediated by its extracellular region. In human colorectal adenocarcinoma Caco-2 cells, integrin α(6)β(4) was localized at hemidesmosomes. Small interfering RNA-mediated suppression of Necl-2 expression enhanced the phorbol ester-induced disruption of the integrin α(6)β(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. |
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Keywords: | Cell Adhesion Epithelial Cell Integrin Phorbol Esters Protein-Protein Interactions Tumor Suppressor Gene CADM1 Necl-2 Hemidesmosome |
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