The diacylglycerol kinase α/atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness.
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 recruiti...
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2014
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oai:doaj.org-article:66b47552bef645f1b45c28e4c5ca2e512021-11-18T08:17:40ZThe diacylglycerol kinase α/atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness.1932-620310.1371/journal.pone.0097144https://doaj.org/article/66b47552bef645f1b45c28e4c5ca2e512014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24887021/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Diacylglycerol 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.Elena RaineroCristina CianflonePaolo Ettore PorporatoFederica ChianaleValeria MalacarneValentina BettioElisa RuffoMichele FerraraFabio BenecchiaDaniela CapelloWolfgang PasterIrene LocatelliAlessandra BertoniNicoletta FilighedduFabiola SinigagliaJim C NormanGianluca BaldanziAndrea GrazianiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e97144 (2014) |
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| topic |
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| spellingShingle |
Medicine R Science Q Elena Rainero Cristina Cianflone Paolo Ettore Porporato Federica Chianale Valeria Malacarne Valentina Bettio Elisa Ruffo Michele Ferrara Fabio Benecchia Daniela Capello Wolfgang Paster Irene Locatelli Alessandra Bertoni Nicoletta Filigheddu Fabiola Sinigaglia Jim C Norman Gianluca Baldanzi Andrea Graziani The diacylglycerol kinase α/atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness. |
| description |
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. |
| format |
article |
| author |
Elena Rainero Cristina Cianflone Paolo Ettore Porporato Federica Chianale Valeria Malacarne Valentina Bettio Elisa Ruffo Michele Ferrara Fabio Benecchia Daniela Capello Wolfgang Paster Irene Locatelli Alessandra Bertoni Nicoletta Filigheddu Fabiola Sinigaglia Jim C Norman Gianluca Baldanzi Andrea Graziani |
| author_facet |
Elena Rainero Cristina Cianflone Paolo Ettore Porporato Federica Chianale Valeria Malacarne Valentina Bettio Elisa Ruffo Michele Ferrara Fabio Benecchia Daniela Capello Wolfgang Paster Irene Locatelli Alessandra Bertoni Nicoletta Filigheddu Fabiola Sinigaglia Jim C Norman Gianluca Baldanzi Andrea Graziani |
| author_sort |
Elena Rainero |
| title |
The diacylglycerol kinase α/atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness. |
| title_short |
The diacylglycerol kinase α/atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness. |
| title_full |
The diacylglycerol kinase α/atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness. |
| title_fullStr |
The diacylglycerol kinase α/atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness. |
| title_full_unstemmed |
The diacylglycerol kinase α/atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness. |
| title_sort |
diacylglycerol kinase α/atypical pkc/β1 integrin pathway in sdf-1α mammary carcinoma invasiveness. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/66b47552bef645f1b45c28e4c5ca2e51 |
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