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

被引：133

作者：

Wolfer, Anita ^{[1
,2
]}

Wittner, Ben S. ^{[1
,2
]}

Irimia, Daniel ^{[1
,3
,4
]}

Flavin, Richard J. ^{[1
,5
]}

Lupien, Mathieu ^{[1
,6
]}

Gunawardane, Ruwanthi N. ^{[1
]}

Meyer, Clifford A. ^{[7
]}

Lightcap, Eric S. ^{[8
]}

Tamayo, Pablo ^{[9
]}

Mesirov, Jill P. ^{[9
]}

Liu, X. Shirley ^{[7
]}

Shioda, Toshi ^{[1
,2
]}

Toner, Mehmet ^{[1
,3
,4
]}

Loda, Massimo ^{[1
,5
,9
]}

Brown, Myles ^{[1
,6
]}

Brugge, Joan S. ^{[1
,9
]}

Ramaswamy, Sridhar ^{[1
,9
,10
]}

机构：

[1] Harvard Univ, Sch Med, Boston, MA 02115 USA

[2] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp E, Ctr Engn Med, Charlestown, MA 02129 USA

[4] Shriners Hosp Children, Boston, MA 02114 USA

[5] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA

[6] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[7] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA

[8] Millennium Pharmaceut Inc, Cambridge, MA 02139 USA

[9] Broad Inst, Cambridge, MA 02142 USA

[10] Harvard Stem Cell Inst, Cambridge, MA 02138 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 08期

基金：

瑞士国家科学基金会;

关键词：

breast cancer; biomarkers; invasion and migration; transcriptional profiling; BREAST-CANCER; C-MYC; MAMMARY TUMORIGENESIS; IN-SITU; GENE; SIGNATURE; ESTROGEN; PROGRESSION; MECHANISMS; MICROARRAY;

D O I：

10.1073/pnas.0914203107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：3698 / 3703

页数：6

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