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.
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.
Honoré
Stéphane
S
UMR-CNRS 6032, Faculté de Pharmacie, Université de la Méditerranée, 27, Bd Jean Moulin 13385 05, Marseille Cedex, France. stephane.honore@pharmacie.univ-mrs.fr
Kovacic
Hervé
H
Pichard
Véronique
V
Briand
Claudette
C
Rognoni
Jean-Baptiste
JB
D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D018938:Caco-2 Cells; D002453:Cell Cycle / Q000502:physiology*; D024141:Collagen Type IV / Q000378:metabolism*; D019925:Cyclin A / Q000378:metabolism; D056741:Cyclin D; D019927:Cyclin E / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D005434:Flow Cytometry; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D024141:Collagen Type IV; D019925:Cyclin A; D056741:Cyclin D; D019927:Cyclin E; D016213:Cyclins; D004791:Enzyme Inhibitors; D038982:Integrin alpha2beta1; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D020928:Mitogen-Activated Protein Kinases