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Título: | Podoplanin mediates ECM degradation by squamous carcinoma cells through control of invadopodia stability |
Autor: | Martín-Villar, Ester CSIC ORCID; Borda-d'Agua, B.; Carrasco-Ramírez, Patricia CSIC; Renart, Jaime CSIC ORCID; Parsons, M.; Quintanilla, Miguel CSIC ORCID; Jones, Gareth E. | Fecha de publicación: | 2015 | Editor: | Nature Publishing Group | Citación: | Oncogene 34(34): 4531-4544 (2015) | Resumen: | Invadopodia are actin-rich cell membrane projections used by invasive cells to penetrate the basement membrane. Control of invadopodia stability is critical for efficient degradation of the extracellular matrix (ECM); however, the underlying molecular mechanisms remain poorly understood. Here, we uncover a new role for podoplanin, a transmembrane glycoprotein closely associated with malignant progression of squamous cell carcinomas (SCCs), in the regulation of invadopodia-mediated matrix degradation. Podoplanin downregulation in SCC cells impairs invadopodia stability, thereby reducing the efficiency of ECM degradation. We report podoplanin as a novel component of invadopodia-associated adhesion rings, where it clusters prior to matrix degradation. Early podoplanin recruitment to invadopodia is dependent on lipid rafts, whereas ezrin/moesin proteins mediate podoplanin ring assembly. Finally, we demonstrate that podoplanin regulates invadopodia maturation by acting upstream of the ROCK-LIMK-Cofilin pathway through the control of RhoC GTPase activity. Thus, podoplanin has a key role in the regulation of invadopodia function in SCC cells, controlling the initial steps of cancer cell invasion. | Descripción: | This work is licensed under a Creative Commons Attribution 4.0 International License. | Versión del editor: | http://dx.doi.org/10.1038/onc.2014.388 | URI: | http://hdl.handle.net/10261/110702 | DOI: | 10.1038/onc.2014.388 | ISSN: | 0950-9232 | E-ISSN: | 1476-5594 |
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