title: Interaction of Necl-4/CADM4 with ErbB3 and integrin α6 β4 and inhibition of ErbB2/ErbB3 signaling and hemidesmosome disassembly.
abstract: Nectin-like molecule 4 (Necl-4)/CADM4, a transmembrane cell-cell adhesion molecule with three Ig-like domains, was shown to serve as a tumor suppressor, but its mode of action has not been elucidated. In this study, we showed that Necl-4 interacted in cis with ErbB3 through their extracellular regions, recruited PTPN13 and inhibited the heregulin-induced activation of the ErbB2/ErbB3 signaling. In addition, we extended our previous finding that Necl-4 interacts in cis with integrin α6 β4 through their extracellular regions and found that Necl-4 inhibited the phorbol ester-induced disassembly of hemidesmosomes. These results indicate that Necl-4 serves as a tumor suppressor by inhibiting the ErbB2/ErbB3 signaling and hemidesmosome disassembly.
authors.affiliation: Division of Molecular and Cellular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Sugiyama
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Mizutani
authors.forename: Souichi
authors.initials: S
authors.lastname: Kurita
authors.forename: Naomasa
authors.initials: N
authors.lastname: Okimoto
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shimono
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
mesh_terms: D018938:Caco-2 Cells; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D057809:HEK293 Cells; D022002:Hemidesmosomes / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000378:metabolism*; D039161:Integrin alpha6beta4 / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D039161:Integrin alpha6beta4; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C498601:CADM4 protein, human; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human