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.

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