Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes

被引：821

作者：

Taube, Joseph H. ^{[2
]}

Herschkowitz, Jason I. ^{[4
]}

Komurov, Kakajan ^{[3
]}

Zhou, Alicia Y. ^{[1
,5
]}

Gupta, Supriya ^{[8
]}

Yang, Jing ^{[6
]}

Hartwell, Kimberly ^{[7
]}

Onder, Tamer T. ^{[1
,5
]}

Gupta, Piyush B. ^{[5
,8
]}

Evans, Kurt W. ^{[2
]}

Hollier, Brett G. ^{[2
]}

Ram, Prahlad T. ^{[3
]}

Lander, Eric S. ^{[1
,5
,8
,9
]}

Rosen, Jeffrey M. ^{[4
]}

Weinberg, Robert A. ^{[1
,5
,10
]}

Mani, Sendurai A. ^{[2
]}

机构：

[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77054 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77054 USA

[4] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[5] MIT, Dept Biol, Cambridge, MA 02142 USA

[6] Univ Calif, Dept Pharmacol, La Jolla, CA 92093 USA

[7] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[8] Broad Inst, Cambridge, MA 02142 USA

[9] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA

[10] MIT, Ludwig Ctr Mol Oncol, Cambridge, MA 02139 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 35期

基金：

美国国家卫生研究院;

关键词：

cancer stem cells; Twist; Snail; FOXC1; TRANSCRIPTION FACTOR SNAIL; CELL-CELL-ADHESION; E-CADHERIN; INDUCED APOPTOSIS; TUMOR-METASTASIS; DOWN-REGULATION; MIR-200; FAMILY; STEM-CELLS; IN-VIVO; SLUG;

D O I：

10.1073/pnas.1004900107

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：

The epithelial-to-mesenchymal transition (EMT) produces cancer cells that are invasive, migratory, and exhibit stem cell characteristics, hallmarks of cells that have the potential to generate metastases. Inducers of the EMT include several transcription factors (TFs), such as Goosecoid, Snail, and Twist, as well as the secreted TGF-beta 1. Each of these factors is capable, on its own, of inducing an EMT in the human mammary epithelial (HMLE) cell line. However, the interactions between these regulators are poorly understood. Overexpression of each of the above EMT inducers up-regulates a subset of other EMT-inducing TFs, with Twist, Zeb1, Zeb2, TGF-beta 1, and FOXC2 being commonly induced. Up-regulation of Slug and FOXC2 by either Snail or Twist does not depend on TGF-beta 1 signaling. Gene expression signatures (GESs) derived by overexpressing EMT-inducing TFs reveal that the Twist GES and Snail GES are the most similar, although the Goosecoid GES is the least similar to the others. An EMT core signature was derived from the changes in gene expression shared by up-regulation of Gsc, Snail, Twist, and TGF-beta 1 and by down-regulation of E-cadherin, loss of which can also trigger an EMT in certain cell types. The EMT core signature associates closely with the claudin-low and metaplastic breast cancer subtypes and correlates negatively with pathological complete response. Additionally, the expression level of FOXC1, another EMT inducer, correlates strongly with poor survival of breast cancer patients.

引用

页码：15449 / 15454

页数：6

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