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Publication : Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis.

First Author  Labelle M Year  2011
Journal  Cancer Cell Volume  20
Issue  5 Pages  576-90
PubMed ID  22094253 Mgi Jnum  J:178954
Mgi Id  MGI:5300667 Doi  10.1016/j.ccr.2011.09.009
Citation  Labelle M, et al. (2011) Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell 20(5):576-90
abstractText  Interactions of cancer cells with the primary tumor microenvironment are important determinants of cancer progression toward metastasis but it is unknown whether additional prometastatic signals are provided during the intravascular transit to the site of metastasis. Here, we show that platelet-tumor cell interactions are sufficient to prime tumor cells for subsequent metastasis. Platelet-derived TGFbeta and direct platelet-tumor cell contacts synergistically activate the TGFbeta/Smad and NF-kappaB pathways in cancer cells, resulting in their transition to an invasive mesenchymal-like phenotype and enhanced metastasis in vivo. Inhibition of NF-kappaB signaling in cancer cells or ablation of TGFbeta1 expression solely in platelets protects against lung metastasis in vivo. Thus, cancer cells rely on platelet-derived signals outside of the primary tumor for efficient metastasis.
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