Overexpression of ADAM9 enhances growth factor-mediated recycling of E-cadherin in human colon cancer cell line HT29 cells.
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.
Hirao
Takafumi
T
Division of Biochemistry and Molecular Genetics, Department of Molecular and Cellular Biology, Ehime University School of Medicine, Ehime 791-0295, Japan.
Nanba
Daisuke
D
Tanaka
Motonari
M
Ishiguro
Hiroshi
H
Kinugasa
Yumi
Y
Doki
Yuichiro
Y
Yano
Masahiko
M
Matsuura
Nariaki
N
Monden
Morito
M
Higashiyama
Shigeki
S
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
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