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Podoplanin Associates with CD44 to Promote Directional Cell Migration

Podoplanin 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 u...

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Autores principales: Martín-Villar, Ester, Fernández-Muñoz, Beatriz, Parsons, Maddy, Yurrita, Maria M., Megías, Diego, Pérez-Gómez, Eduardo, Jones, Gareth E., Quintanilla, Miguel
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002391/
https://www.ncbi.nlm.nih.gov/pubmed/20962267
http://dx.doi.org/10.1091/mbc.E10-06-0489
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author Martín-Villar, Ester
Fernández-Muñoz, Beatriz
Parsons, Maddy
Yurrita, Maria M.
Megías, Diego
Pérez-Gómez, Eduardo
Jones, Gareth E.
Quintanilla, Miguel
author_facet Martín-Villar, Ester
Fernández-Muñoz, Beatriz
Parsons, Maddy
Yurrita, Maria M.
Megías, Diego
Pérez-Gómez, Eduardo
Jones, Gareth E.
Quintanilla, Miguel
author_sort Martín-Villar, Ester
collection PubMed
description Podoplanin 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.
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spelling pubmed-30023912011-03-02 Podoplanin Associates with CD44 to Promote Directional Cell Migration Martín-Villar, Ester Fernández-Muñoz, Beatriz Parsons, Maddy Yurrita, Maria M. Megías, Diego Pérez-Gómez, Eduardo Jones, Gareth E. Quintanilla, Miguel Mol Biol Cell Articles Podoplanin 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. The American Society for Cell Biology 2010-12-15 /pmc/articles/PMC3002391/ /pubmed/20962267 http://dx.doi.org/10.1091/mbc.E10-06-0489 Text en © 2010 by The American Society for Cell Biology This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
spellingShingle Articles
Martín-Villar, Ester
Fernández-Muñoz, Beatriz
Parsons, Maddy
Yurrita, Maria M.
Megías, Diego
Pérez-Gómez, Eduardo
Jones, Gareth E.
Quintanilla, Miguel
Podoplanin Associates with CD44 to Promote Directional Cell Migration
title Podoplanin Associates with CD44 to Promote Directional Cell Migration
title_full Podoplanin Associates with CD44 to Promote Directional Cell Migration
title_fullStr Podoplanin Associates with CD44 to Promote Directional Cell Migration
title_full_unstemmed Podoplanin Associates with CD44 to Promote Directional Cell Migration
title_short Podoplanin Associates with CD44 to Promote Directional Cell Migration
title_sort podoplanin associates with cd44 to promote directional cell migration
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002391/
https://www.ncbi.nlm.nih.gov/pubmed/20962267
http://dx.doi.org/10.1091/mbc.E10-06-0489
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