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Title

Podoplanin associates with CD44 to promote directional cell migration

AuthorsMartín-Villar, Ester ; Fernández-Muñoz, Beatriz ; Yurrita, María M. ; Megías, Diego; Pérez-Gómez, Eduardo ; Quintanilla, Miguel
Issue Date15-Dec-2010
PublisherAmerican Society for Cell Biology
CitationMolecular Biology of the Cell 21(24): 4387-4399 (2010)
AbstractPodoplanin is a transmembrane glycoprotein up-regulated in different human tumors, especially those derived from squamous stratified epithelia (SCCs). Its expression in tumor cells is linked to increased cell migration and invasiveness; however, the mechanisms underlying this process remain poorly understood. Here we report that CD44, the major hyaluronan (HA) receptor, is a novel partner for podoplanin. Expression of the CD44 standard isoform (CD44s) is coordinately up-regulated together with that of podoplanin during progression to highly aggressive SCCs in a mouse skin model of carcinogenesis, and during epithelial-mesenchymal transition (EMT). In carcinoma cells, CD44 and podoplanin colocalize at cell surface protrusions. Moreover, CD44 recruitment promoted by HA-coated beads or cross-linking with a specific CD44 antibody induced corecruitment of podoplanin. Podoplanin-CD44s interaction was demonstrated both by coimmunoprecipitation experiments and, in vivo, by fluorescence resonance energy transfer/fluorescence lifetime imaging microscopy (FRET/FLIM), the later confirming its association on the plasma membrane of cells with a migratory phenotype. Importantly, we also show that podoplanin promotes directional persistence of motility in epithelial cells, a feature that requires CD44, and that both molecules cooperate to promote directional migration in SCC cells. Our results support a role for CD44-podoplanin interaction in driving tumor cell migration during malignancy.
DescriptionThis article is under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.-- et al.
Publisher version (URL)http://dx.doi.org/10.1091/mbc.E10-06-0489
URIhttp://hdl.handle.net/10261/37839
DOI10.1091/mbc.E10-06-0489
E-ISSN1939-4586
Appears in Collections:(IIBM) Artículos
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