title: Interaction of nectin-like molecule 2 with integrin alpha6beta4 and inhibition of disassembly of integrin alpha6beta4 from hemidesmosomes.
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.
authors: Division of Molecular and Cellular Biology, Department of Biochemistry, and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Hyogo, Japan.
authors: Kiyohito
authors: K
authors: Mizutani
authors: Satoshi
authors: S
authors: Kawano
authors: Akihiro
authors: A
authors: Minami
authors: Masazumi
authors: M
authors: Waseda
authors: Wataru
authors: W
authors: Ikeda
authors: Yoshimi
authors: Y
authors: Takai
mesh_terms: D018938:Caco-2 Cells; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D022002:Hemidesmosomes / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D039161:Integrin alpha6beta4 / Q000235:genetics / Q000378:metabolism*; D039663:Integrin beta4 / Q000235:genetics / Q000378:metabolism; D007797:Laminin / Q000096:biosynthesis / Q000235:genetics; D011485:Protein Binding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D039161:Integrin alpha6beta4; D039663:Integrin beta4; D007797:Laminin; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C403514:CADM1 protein, human; C508053:ERBB2 protein, human