Research ArticleCancer Biology

Phosphoproteomic analysis of interacting tumor and endothelial cells identifies regulatory mechanisms of transendothelial migration

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Science Signaling  09 Feb 2016:
Vol. 9, Issue 414, pp. ra15
DOI: 10.1126/scisignal.aac5820

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Phosphoproteomics of metastasis

During the process of metastasis, cancer cells migrate into and then out of the bloodstream to colonize the target tissue. Locard-Paulet et al. investigated signaling events that occurred when breast cancer cells were cocultured with endothelial cells to mimic the early events associated with exit from the bloodstream. Detailed analysis of the phosphorylation status of a specific site on the receptor EPHA2, which can mediate cell repulsion or attraction, showed decreased phosphorylation of that site in cancer cells upon endothelial contact. Phosphorylation of this site was found to be critical for EPHA2-mediated inhibition of transendothelial migration. Furthermore, a highly metastatic breast cancer cell line that targets the lung exhibited altered phosphorylation dynamics at this site and had enhanced adhesion to and migration through endothelial cell monolayers in culture. Thus, this study provides a rich source of candidates for exploration of cancer cell metastasis and identifies altered phosphorylation dynamics of EPHA2 as a mechanism that may enhance breast cancer cell exit from the bloodstream.

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