2024-03-29T00:48:06Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/378392021-12-28T16:44:00Zcom_10261_22com_10261_1col_10261_275
00925njm 22002777a 4500
dc
Martín-Villar, Ester
author
Fernández-Muñoz, Beatriz
author
Yurrita, María M.
author
Megías, Diego
author
Pérez-Gómez, Eduardo
author
Quintanilla, Miguel
author
2010-12-15
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.
Molecular Biology of the Cell 21(24): 4387-4399 (2010)
http://hdl.handle.net/10261/37839
10.1091/mbc.E10-06-0489
1939-4586
20962267
Podoplanin associates with CD44 to promote directional cell migration