Tumor invasion in the absence of epithelial-mesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton

Andreas Wicki; François Lehembre; Nikolaus Wick; Brigitte Hantusch; Dontscho Kerjaschki; Gerhard Christofori

doi:10.1016/j.ccr.2006.03.010

Tumor invasion in the absence of epithelial-mesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton

Cancer Cell. 2006 Apr;9(4):261-72. doi: 10.1016/j.ccr.2006.03.010.

Authors

Andreas Wicki¹, François Lehembre, Nikolaus Wick, Brigitte Hantusch, Dontscho Kerjaschki, Gerhard Christofori

Affiliation

¹ Institute of Biochemistry and Genetics, Department of Clinical-Biological Sciences, Center of Biomedicine, University of Basel, 4058 Basel, Switzerland.

PMID: 16616332
DOI: 10.1016/j.ccr.2006.03.010

Abstract

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).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / metabolism*
Animals
Cadherins / genetics
Cadherins / metabolism
Cell Line, Tumor
Cell Movement
Cytoskeleton / metabolism*
DNA-Binding Proteins / metabolism
Disease Progression
Down-Regulation
Epithelial Cells / metabolism
Epithelial Cells / pathology*
GTPase-Activating Proteins / genetics
GTPase-Activating Proteins / metabolism
Gene Expression Regulation, Neoplastic
Humans
Leukemia, B-Cell / metabolism
Leukemia, B-Cell / pathology
Membrane Glycoproteins / metabolism*
Mesoderm / metabolism
Mesoderm / pathology*
Mice
Mice, Transgenic
Neoplasm Invasiveness / genetics
Neoplasm Invasiveness / pathology
Organic Cation Transport Proteins / metabolism
Pseudopodia / metabolism
Transcription Factors / metabolism
cdc42 GTP-Binding Protein / metabolism
rhoA GTP-Binding Protein / metabolism

Substances

Actins
Cadherins
DNA-Binding Proteins
ETV5 protein, human
Etv5 protein, mouse
GTPase-Activating Proteins
Gp38 protein, mouse
Membrane Glycoproteins
Organic Cation Transport Proteins
PDPN protein, human
Ralbp1 protein, mouse
Transcription Factors
solute carrier family 22 (organic cation transporter), member 3
cdc42 GTP-Binding Protein
rhoA GTP-Binding Protein