E-cadherin/p120-catenin and tetraspanin Co-029 cooperate for cell motility control in human colon carcinoma.
Tumor invasion and metastasis are major obstacles to clinical treatment that rely on cell migration. Here, we elucidate a mechanism of colon carcinoma cell migration that is supported by the cell surface tetraspanin Co-029 (tspan8), which is known to favor tumor progression and metastasis. This mechanism is unmasked by silencing of E-cadherin or its associated adapter molecule p120-catenin (p120ctn), and it involves a switch in signaling between the collagen-binding integrins α(1)β(1) and α(2)β(1). Direct interaction between E-cadherin and Co-029 was documented by chemical cross-linking and immunohistologic analysis of colon carcinomas. High expression of Co-029 and cytoplasmic delocalization of p120ctn were each associated with poor prognosis. Cell motility was reduced severely by antibody-mediated disruption of Co-029 only when p120ctn was silenced, suggesting that tumor progression may be hindered by Co-029 targeting. Our findings define a function for tetraspanin Co-029 as a modifier of cancer cell motility and reveal an adhesion signaling network implicated in progression and metastasis.
Greco
Céline
C
Inserm, U602, Villejuif, France.
Bralet
Marie-Pierre
MP
Ailane
Naouel
N
Dubart-Kupperschmitt
Anne
A
Rubinstein
Eric
E
Le Naour
François
F
Boucheix
Claude
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D038982:Integrin alpha2beta1 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction; D059470:Tetraspanins; D014161:Transduction, Genetic; D000095002:Delta Catenin
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015820:Cadherins; D051177:Catenins; D038982:Integrin alpha2beta1; D008562:Membrane Glycoproteins; C065609:TSPAN8 protein, human; D059470:Tetraspanins; D020558:GTP Phosphohydrolases; D000095002:Delta Catenin