rho‐mediated protein tyrosine phosphorylation in lysophosphatidic‐acid‐induced tumor‐cell invasion

• Published in: International journal of cancer Vol. 65; no. 5; pp. 627 - 632
• Main Authors: Imamura, Fumio, Shinkai, Kiyoko, Mukai, Mutsuko, Yoshioka, Kiyoko, Komagome, Rika, Iwasaki, Teruo, Akedo, Hitoshi
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01.03.1996; Wiley-Liss
• Subjects: Animals; Biological and medical sciences; Cell Adhesion Molecules - metabolism; Cytoskeletal Proteins - metabolism; Enzyme Inhibitors - pharmacology; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Gastroenterology. Liver. Pancreas. Abdomen; Genistein; GTP-Binding Proteins - metabolism; Isoflavones - pharmacology; Liver Neoplasms, Experimental - metabolism; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Lysophospholipids - pharmacology; Medical sciences; Neoplasm Invasiveness; Paxillin; Phosphoproteins - metabolism; Phosphorylation; Phosphotyrosine - metabolism; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; Rats; rho GTP-Binding Proteins; Signal Transduction; Tumor Cells, Cultured; Tumors; Tyrosine; Phosphorylation; Carcinoma; Pathophysiology; Rat; Liver; Rodentia; Hepatic disease; Exploration; Metastasis; Malignant tumor; In vitro; Invasion; Vertebrata; Mammalia; Malignant effusion; Animal; Digestive diseases; Ascites; Tumor cell; Peritoneum
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19960301)65:5<627::AID-IJC12>3.0.CO;2-4

Rat ascites hepatoma cells (MMI) invade a mesothelial cell monolayer in vitro in assay medium containing serum, but not in serum‐free medium. Serum could be completely replaced by I‐oleoyl lysophosphatidic acid (LPA) in inducing invasion. LPA‐induced invasion was inhibited by genistein, a tyrosine‐kinase inhibitor. Protein tyrosine phosphorylation in response to LPA was thus analyzed in order to determine the molecular mechanism of invasion. LPA of invasion‐inducible concentrations evoked a transient increase in tyrosine phosphorylation, mainly of 110‐ to 130‐kDa proteins in MMI cells but not in mesothelial cells. These concentrations of LPA were over 10 times higher (10 to 25 μM) than those necessary to produce a variety of biological actions, such as tyrosine phosphorylation in fibroblasts, neurite retraction and platelet aggregation. Protein tyrosine phosphorylation and invasion by MMI cells induced by LPA are largely regulated by rho p21, because both were inhibited by Clostridium botulinum C3 exo‐enzyme, which is known to specifically inactivate rho p21. Invasion of MCL by MMI cells induced by serum and that by B16FE7 cells induced by LPA were inhibited by genistein or C3 as well. By immunoprecipitation, we detected p125 focal adhesion kinase (FAK) as a major protein of 110‐ to 130‐kDa tyrosine phosphorylated in response to LPA. Tyrosine phosphorylation of paxillin by LPA was also detected. © 1996 Wiley‐Liss, Inc.