MYC regulation of a "poor-prognosis" metastatic cancer cell state.

Abstract

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.

• Authors: Anita Wolfer, Ben S Wittner, Daniel Irimia, Richard J 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
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 107 Issue 8 Pg. 3698-703 (Feb 23 2010) ISSN: 1091-6490 [Electronic] United States
• PMID: 20133671 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Biomarkers, Tumor
• Proto-Oncogene Proteins c-myc

Topics

• Biomarkers, Tumor (genetics)
• Breast Neoplasms (genetics, pathology)
• Cell Movement (genetics)
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Neoplasm Metastasis
• Oligonucleotide Array Sequence Analysis
• Prognosis
• Proto-Oncogene Proteins c-myc (metabolism)