Alpha2beta1-integrin signaling by itself controls G1/S transition in a human adenocarcinoma cell line (Caco-2): implication of NADPH oxidase-dependent production of ROS.

Abstract

In this work, we report that type IV collagen, mainly via alpha2beta1-integrin ligation, was able to induce cyclin expression and G1/S transition in a colic adenocarcinoma cell line (Caco-2) cultured without soluble growth factors or fetal bovine serum. This process involved Erk 1/2 activation and the production of reactive oxygen species (ROS) by a membrane-bound NADPH oxidase. Data presented here show that NADPH oxidase-dependent production of ROS increased following alpha2beta1-integrin ligation with type IV collagen or with a specific monoclonal antibody (Gi9 mAb). NADPH oxidase activation and, therefore, the production of ROS were shown to be involved in the increase of alpha2beta1-integrin plasma membrane expression, p38 MAPK phosphorylation, cyclin expression, and G1/S transition. We thus identified in this work a new integrin-signaling pathway in colon tumor cells involved in cell cycle regulation by the extracellular matrix.

• Authors: Stéphane Honoré, Hervé Kovacic, Véronique Pichard, Claudette Briand, Jean-Baptiste Rognoni
• Journal: Experimental cell research (Exp Cell Res) Vol. 285 Issue 1 Pg. 59-71 (Apr 15 2003) ISSN: 0014-4827 [Print] United States
• PMID: 12681287 (Publication Type: Journal Article)

Chemical References

• Collagen Type IV
• Cyclin A
• Cyclin D
• Cyclin E
• Cyclins
• Enzyme Inhibitors
• Integrin alpha2beta1
• Reactive Oxygen Species
• NADPH Oxidases
• Protein-Tyrosine Kinases
• Focal Adhesion Kinase 1
• Focal Adhesion Protein-Tyrosine Kinases
• PTK2 protein, human
• Mitogen-Activated Protein Kinases

Topics

• Adenocarcinoma (metabolism)
• Animals
• Caco-2 Cells
• Cell Cycle (physiology)
• Collagen Type IV (metabolism)
• Cyclin A (metabolism)
• Cyclin D
• Cyclin E (metabolism)
• Cyclins (metabolism)
• Enzyme Activation
• Enzyme Inhibitors (metabolism)
• Flow Cytometry
• Focal Adhesion Kinase 1
• Focal Adhesion Protein-Tyrosine Kinases
• Humans
• Integrin alpha2beta1 (metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• NADPH Oxidases (metabolism)
• Protein-Tyrosine Kinases (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (physiology)