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.
Wolfer
Anita
A
Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.
Wittner
Ben S
BS
Irimia
Daniel
D
Flavin
Richard J
RJ
Lupien
Mathieu
M
Gunawardane
Ruwanthi N
RN
Meyer
Clifford A
CA
Lightcap
Eric S
ES
Tamayo
Pablo
P
Mesirov
Jill P
JP
Liu
X Shirley
XS
Shioda
Toshi
T
Toner
Mehmet
M
Loda
Massimo
M
Brown
Myles
M
Brugge
Joan S
JS
Ramaswamy
Sridhar
S
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