MYC regulation of a "poor-prognosis" metastatic cancer cell state.
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.
Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.
Anita
A
Wolfer
Ben S
BS
Wittner
Daniel
D
Irimia
Richard J
RJ
Flavin
Mathieu
M
Lupien
Ruwanthi N
RN
Gunawardane
Clifford A
CA
Meyer
Eric S
ES
Lightcap
Pablo
P
Tamayo
Jill P
JP
Mesirov
X Shirley
XS
Liu
Toshi
T
Shioda
Mehmet
M
Toner
Massimo
M
Loda
Myles
M
Brown
Joan S
JS
Brugge
Sridhar
S
Ramaswamy
D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*
D014408:Biomarkers, Tumor; D016271:Proto-Oncogene Proteins c-myc