MYC suppresses cancer metastasis by direct transcriptional silencing of αv and β3 integrin subunits

被引：159

作者：

Liu, Hong ^{[1
]}

Radisky, Derek C. ^{[2
]}

Yang, Dun ^{[1
]}

Xu, Ren ^{[3
]}

Radisky, Evette S. ^{[2
]}

Bissell, Mina J. ^{[3
]}

Bishop, J. Michael ^{[1
]}

机构：

[1] Univ Calif San Francisco, George Williams Hooper Fdn, San Francisco, CA 94143 USA

[2] Mayo Clin, Ctr Canc, Jacksonville, FL 32224 USA

[3] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Life Sci Div, Berkeley, CA 94720 USA

来源：

NATURE CELL BIOLOGY | 2012年 / 14卷 / 06期

关键词：

C-MYC; TRANSGENIC MICE; BREAST-CANCER; CELL INVASION; EXPRESSION; ONCOGENE; MIGRATION; GENES; TRANSFORMATION; PROLIFERATION;

D O I：

10.1038/ncb2491

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Overexpression of MYC transforms cells in culture, elicits malignant tumours in experimental animals and is found in many human tumours. We now report the paradoxical finding that this powerful oncogene can also act as a suppressor of cell motility, invasiveness and metastasis. Overexpression of MYC stimulated proliferation of breast cancer cells both in culture and in vivo as expected, but inhibited motility and invasiveness in culture, and lung and liver metastases in xenografted tumours. We show further that MYC represses transcription of both subunits of alpha(v),beta(3) integrin, and that exogenous expression of beta(3) integrin in human breast cancer cells that do not express this integrin rescues invasiveness and migration when MYC is downregulated. These data uncover an unexpected function of MYC, provide an explanation for the hitherto puzzling literature on the relationship between MYC and metastasis, and reveal a variable that could influence the development of therapies that target MYC.

引用

页码：567 / +

页数：13

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