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MYC regulation of a “poor-prognosis” metastatic cancer cell state

2010; National Academy of Sciences; Volume: 107; Issue: 8 Linguagem: Inglês

10.1073/pnas.0914203107

1091-6490

Anita Wolfer, Ben S. Wittner, Daniel Irimia, Richard Flavin, Mathieu Lupien, Ruwanthi N. Gunawardane, Clifford A. Meyer, Eric S. Lightcap, Pablo Tamayo, Jill P. Mesirov, X. Shirley Liu, Toshi Shioda, Mehmet Toner, Massimo Loda, Myles Brown, Joan S. Brugge, Sridhar Ramaswamy,

Cancer-related Molecular Pathways

Gene expression signatures are used in the clinic as prognostic tools to determine the risk of individual patients with localized breast tumors developing distant metastasis. We lack a clear understanding, however, of whether these correlative biomarkers link to a common biological network that regulates metastasis. We find that the c-MYC oncoprotein coordinately regulates the expression of 13 different “poor-outcome” cancer signatures. In addition, functional inactivation of MYC in human breast cancer cells specifically inhibits distant metastasis in vivo and invasive behavior in vitro of these cells. These results suggest that MYC oncogene activity (as marked by “poor-prognosis” signature expression) may be necessary for the translocation of poor-outcome human breast tumors to distant sites.