title: Overexpression of ADAM9 enhances growth factor-mediated recycling of E-cadherin in human colon cancer cell line HT29 cells.
abstract: Growth factor-mediated stimulation of epithelial cells induces the disassembly of E-cadherin-mediated cell-cell adhesion. We found that overexpression of a disintegrin and metalloprotease 9 (ADAM9) enhanced growth factor-mediated induction of endocytosis and dynamic recycling of E-cadherin in HT29 human colon cancer cells. In addition, ubiquitination and degradation of E-cadherin were reduced in these cells. ADAM9 constitutively interacted with E-cadherin, and the two proteins co-localized at the plasma membrane of HT29 cells. Administration of a metalloprotease inhibitor or overexpression of an ADAM9 mutant lacking metalloprotease activity attenuated growth factor-dependent endocytosis and recycling of E-cadherin as well as scattering of HT29 cells. These results suggest that the metalloprotease activity of ADAM9 mediates growth factor-induced endocytosis and dynamic recycling of E-cadherin and prevents E-cadherin degradation.
authors.affiliation: Division of Biochemistry and Molecular Genetics, Department of Molecular and Cellular Biology, Ehime University School of Medicine, Ehime 791-0295, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Hirao
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nanba
authors.forename: Motonari
authors.initials: M
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishiguro
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kinugasa
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yano
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
authors.forename: Shigeki
authors.initials: S
authors.lastname: Higashiyama
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004705:Endocytosis; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D019073:HT29 Cells; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D045726:Metalloproteases / Q000378:metabolism; D009154:Mutation; D025801:Ubiquitin / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015820:Cadherins; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D025801:Ubiquitin; D004815:Epidermal Growth Factor; D045726:Metalloproteases; D051722:ADAM Proteins; C098339:ADAM9 protein, human