Posted by: Dan | June 6, 2006

Tumor invasion, minus the EMT

Just a short comment here on a new paper from Gerhard Christofori’s lab, published in Cancer Research, titled Tumor invasion in the absence of epithelial-mesenchymal transition: Podoplanin-mediated remodeling of the actin cytoskeleton.

In the paper, they identify a molecular pathway that facilitates collective cell invasion of tumor cells in a manner that vaguely resembles migration in development, where a sheet of cells move together for gastrulation, neural crest formation, etc. Wicki et al. found that Podoplanin expression at the invasive front of a tumor induces filopodia formation by modulating Rho-family GTPases, in a process where cell-cell junctions mediated by E-cadherin are retained. I quote the paper’s significance below the fold.

In most epithelial cancers, the expression of E-cadherin is lost during the transition from adenoma to carcinoma. Here, we report a molecular pathway of tumor progression that does not involve the loss of E-cadherin function or epithelial-mesenchymal transition: podoplanin, which is frequently upregulated in the invasive front of human cancers, induces tumor cell migration and invasion in breast cancer cells in vitro and in a mouse model of tumorigenesis in vivo without dissolving E-cadherin-mediated junctional complexes. Podoplanin induces the formation of filopodia by modulating the activities of Rho-family GTPases, which ultimately leads to collective cell invasion, a phenotype often observed in human carcinoma. These results raise important questions about diagnosing malignant disease and designing adequate antimetastatic therapies.

Indeed – and not only does it raise a number of questions, it provides a nice example of yet another “rule” of cancer progression that is more of a “guideline.”

Reference:

  • Tumor invasion in the absence of epithelial-mesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton. Wicki A, Lehembre F, Wick N, Hantusch B, Kerjaschki D, Christofori G. Cancer Cell. 2006 Apr; 9(4):261-72. Pubmed

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