E-Cadherin/p120-Catenin and Tetraspanin Co-029 Cooperate for Cell Motility Control in Human Colon Carcinoma

• Published in: Cancer research (Chicago, Ill.) Vol. 70; no. 19; pp. 7674 - 7683
• Main Authors: GRECO, Céline, BRALET, Marie-Pierre, AILANE, Naouel, DUBART-KUPPERSCHMITT, Anne, RUBINSTEIN, Eric, LE NAOUR, François, BOUCHEIX, Claude
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.10.2010
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antigens, Neoplasm - biosynthesis; Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; Antigens, Neoplasm - metabolism; Antineoplastic agents; Biological and medical sciences; Cadherins - metabolism; Catenins - metabolism; Cell Line, Tumor; Cell Movement - physiology; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Gastroenterology. Liver. Pancreas. Abdomen; GTP Phosphohydrolases - metabolism; Humans; Immunohistochemistry; Integrin alpha2beta1 - metabolism; Medical sciences; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred BALB C; Pharmacology. Drug treatments; Signal Transduction; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tetraspanins; Transduction, Genetic; Tumors; Human; Cell adhesion molecule; Malignant tumor; Colonic disease; Cell motility; Control; Colon cancer; Digestive diseases; Intestinal disease; Colon carcinoma; E Cadherin; Catenin; Cancer; Tetraspanin
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-09-4482

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.