alpha v beta 5/beta 6 integrin suppression leads to a stimulation of alpha 2 beta 1 dependent cell migration resistant to PI3K/Akt inhibition
| Autor: | Véronique Rigot, Céline Defilles, Jean-Claude Lissitzky, Estelle Delamarre, Naziha Marrakchi, Marie-Pierre Montero, Charles Prévôt, Frédéric André, José Luis |
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| Přispěvatelé: | Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), This work was financially supported by institutional grants from the CNRS, INSERM and Aix-Marseille University and specific grants from 'Cancéropôle Provence Alpes Côte d'Azur'., The authors wish to thank Dr. S.L. Goodman for his gift of the mouse mAb 17E6 against human αv integrin (Darmstadt, Germany), and C. Siret, J. Secchi and G. Capriolo for their technical assistance., Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
MESH: Signal Transduction
Integrins Alpha-v beta-5 [SDV]Life Sciences [q-bio] MESH: RNA Small Interfering/genetics MESH: Oncogene Protein v-akt/antagonists & inhibitors PI3K MESH: Cell Movement/drug effects chemistry.chemical_compound 0302 clinical medicine MESH: Integrins/physiology PKC Colon adenocarcinoma Crosstalk 0303 health sciences MESH: Phosphatidylinositol 3-Kinases/antagonists & inhibitors Cell migration MESH: Antigens Neoplasm/physiology MESH: Antigens Neoplasm/genetics MESH: Receptors Vitronectin/physiology 3. Good health Cell biology 030220 oncology & carcinogenesis MESH: Integrin alpha2beta1/physiology Signal transduction Cell signaling MESH: Cell Line Tumor Integrin MESH: Cell Movement/physiology Biology MESH: Receptors Vitronectin/genetics Focal adhesion MESH: Protein Kinase Inhibitors/pharmacology 03 medical and health sciences MESH: Collagen Type I/metabolism MESH: Integrins/genetics Protein kinase B PI3K/AKT/mTOR pathway MESH: Integrin alpha2beta1/antagonists & inhibitors MESH: Oncogene Protein v-akt/physiology 030304 developmental biology MESH: Humans MESH: Receptors Vitronectin/antagonists & inhibitors MESH: Integrins/antagonists & inhibitors MESH: Focal Adhesions MESH: Oncogene Protein v-akt/genetics Cell Biology MESH: Phosphatidylinositol 3-Kinases/physiology Integrin signaling chemistry biology.protein MESH: Integrin alpha2beta1/genetics |
| Zdroj: | Experimental Cell Research Experimental Cell Research, Elsevier, 2009, 315 (11), pp.1840-1849. ⟨10.1016/j.yexcr.2009.03.014⟩ |
| ISSN: | 0014-4827 1090-2422 |
| DOI: | 10.1016/j.yexcr.2009.03.014⟩ |
| Popis: | Crosstalk between integrins is involved in the regulation of various cell functions including cell migration. Here we identify the interplay between the integrins alpha v beta 5/beta 6 and alpha 2 beta 1 during cell migration toward type I collagen. Human colon cancer cell lines HT29-D4 and SW480 were used as cell models. To improve our Understanding of the consequences of alpha v beta 5/beta 6 function on alpha 2 beta 1, we decreased the expression of alpha v integrins by either siRNA or lysosomal targeting strategies, or inhibited their function using, as antagonists, blocking antibodies or disintegrins. In all cases, we observed a greatly enhanced alpha 2 beta 1 integrin-dependent cell migration associated with focal adhesion rearrangements and increased outside-in signaling as demonstrated by elevated phosphorylation of focal adhesion kinase and MAPKinase (ERK1 and ERK2). The alpha v beta 5/beta 6-dependent limitation of alpha 2 beta 1 function could be overridden by TS2/16, an activating anti-beta 1 antibody. Interestingly, compared to control cells, the pharmacological inhibition of PI3Kinase or the siRNA-mediated knockdown of AKT had little effect on the high alpha 2 beta 1-mediated cell migration observed in the absence of alpha v integrins or following activation of alpha 2 beta 1 integrins by the TS2/16. These results suggest that integrins alpha v beta 5/beta 6 repress alpha 2 beta 1 possibly by interfering with their activation process and thereby modify the cell signaling regulation of alpha 2 beta 1-mediated migration. (C) 2009 Elsevier Inc. All rights reserved. |
| Databáze: | OpenAIRE |
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