The diacylglycerol kinase α/atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness
| Autor: | Elena Rainero, Nicoletta Filigheddu, Cristina Cianflone, Valeria Malacarne, Gianluca Baldanzi, Jim C. Norman, Irene Locatelli, Fabiola Sinigaglia, Wolfgang Paster, Daniela Capello, Fabio Benecchia, Valentina Bettio, Federica Chianale, Alessandra Bertoni, Andrea Graziani, Elisa Ruffo, Paolo E. Porporato, Michele Ferrara |
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| Přispěvatelé: | Rainero, Elena, Cianflone, Cristina, Porporato, Paolo Ettore, Chianale, Federica, Malacarne, Valeria, Bettio, Valentina, Ruffo, Elisa, Ferrara, Michele, Benecchia, Fabio, Capello, Daniela, Paster, Wolfgang, Locatelli, Irene, Bertoni, Alessandra, Filigheddu, Nicoletta, Sinigaglia, Fabiola, Norman, Jim C., Baldanzi, Gianluca, Graziani, Andrea, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Genetics and Molecular Biology (all)
Cell signaling Signal transduction Biochemistry Epithelium Metastasis Biochemistry Genetics and Molecular Biology (all) Agricultural and Biological Sciences (all) Molecular Cell Biology Basic Cancer Research Medicine and Health Sciences Pseudopodia Cytoskeleton Second Messenger System Protein Kinase C Multidisciplinary Integrin beta1 Medicine (all) Mechanisms of Signal Transduction Cell migration Lipids Signaling Cascades Cell biology rac GTP-Binding Proteins Rac GTP-Binding Proteins Protein Transport Oncology Matrix Metalloproteinase 9 Medicine Female Anatomy Cellular Structures and Organelles Breast Neoplasm Research Article Human Signal Transduction Diacylglycerol Kinase Science Integrin Lipid signaling Breast Neoplasms Phosphoinositide Signal Transduction Biology Oncogenic signaling Lipid Mediators Cell Line Tumor Humans Neoplasm Invasiveness rac GTP-Binding Protein Protein kinase C Diacylglycerol kinase Neoplasm Invasivene Biology and life sciences Antigens CD29 Epithelial Cells Protein kinase C signaling Chemokine CXCL12 Biological Tissue Cell movement signaling Phospholipid Signaling Cascade biology.protein |
| Zdroj: | PLoS ONE, Vol 9, Iss 6, p e97144 (2014) PLoS One, Vol. 9, no. 6, p. e97144 (2014) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0097144&representation=PDF |
| Popis: | Diacylglycerol kinase α (DGKα), by phosphorylating diacylglycerol into phosphatidic acid, provides a key signal driving cell migration and matrix invasion. We previously demonstrated that in epithelial cells activation of DGKα activity promotes cytoskeletal remodeling and matrix invasion by recruiting atypical PKC at ruffling sites and by promoting RCP-mediated recycling of α5β1 integrin to the tip of pseudopods. In here we investigate the signaling pathway by which DGKα mediates SDF-1α-induced matrix invasion of MDA-MB-231 invasive breast carcinoma cells. Indeed we showed that, following SDF-1α stimulation, DGKα is activated and localized at cell protrusion, thus promoting their elongation and mediating SDF-1α induced MMP-9 metalloproteinase secretion and matrix invasion. Phosphatidic acid generated by DGKα promotes localization at cell protrusions of atypical PKCs which play an essential role downstream of DGKα by promoting Rac-mediated protrusion elongation and localized recruitment of β1 integrin and MMP-9. We finally demonstrate that activation of DGKα, atypical PKCs signaling and β1 integrin are all essential for MDA-MB-231 invasiveness. These data indicates the existence of a SDF-1α induced DGKα - atypical PKC - β1 integrin signaling pathway, which is essential for matrix invasion of carcinoma cells. © 2014 Rainero et al. |
| Databáze: | OpenAIRE |
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