Tumor invasion in the absence of epithelial-mesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton.
The expression of podoplanin, a small mucin-like protein, is upregulated in the invasive front of a number of human carcinomas. We have investigated podoplanin function in cultured human breast cancer cells, in a mouse model of pancreatic beta cell carcinogenesis, and in human cancer biopsies. Our results indicate that podoplanin promotes tumor cell invasion in vitro and in vivo. Notably, the expression and subcellular localization of epithelial markers are unaltered, and mesenchymal markers are not induced in invasive podoplanin-expressing tumor cells. Rather, podoplanin induces collective cell migration by filopodia formation via the downregulation of the activities of small Rho family GTPases. In conclusion, podoplanin induces an alternative pathway of tumor cell invasion in the absence of epithelial-mesenchymal transition (EMT).
Wicki
Andreas
A
Institute of Biochemistry and Genetics, Department of Clinical-Biological Sciences, Center of Biomedicine, University of Basel, 4058 Basel, Switzerland.
Lehembre
François
F
Wick
Nikolaus
N
Hantusch
Brigitte
B
Kerjaschki
Dontscho
D
Christofori
Gerhard
G
D000199:Actins / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015448:Leukemia, B-Cell / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000099254:Organic Cation Transporter 3; D000098853:Podoplanin
D000199:Actins; D015820:Cadherins; D004268:DNA-Binding Proteins; D020690:GTPase-Activating Proteins; D008562:Membrane Glycoproteins; D027701:Organic Cation Transport Proteins; D014157:Transcription Factors; D020764:cdc42 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; D000099254:Organic Cation Transporter 3; C086680:ETV5 protein, human; C513242:Etv5 protein, mouse; C490441:Pdpn protein, mouse; D000098853:Podoplanin; C117468:PDPN protein, human; C490620:Ralbp1 protein, mouse