A Gene Expression Signature Associated with "K-Ras Addiction" Reveals Regulators of EMT and Tumor Cell Survival

被引：668

作者：

Singh, Anurag ^{[1
,2
]}

Greninger, Patricia ^{[1
,2
]}

Rhodes, Daniel ^{[3
,4
]}

Koopman, Louise ^{[5
]}

Violette, Sheila ^{[6
]}

Bardeesy, Nabeel ^{[1
,2
]}

Settleman, Jeff ^{[1
,2
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA

[2] Harvard Univ, Sch Med, Charlestown, MA 02129 USA

[3] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Sch Med, Dept Bioinformat, Ann Arbor, MI 48109 USA

[5] Biogen Idec Inc, Dept Discovery Oncol, Cambridge, MA 02142 USA

[6] Stromedix Inc, Cambridge, MA 02141 USA

来源：

CANCER CELL | 2009年 / 15卷 / 06期

关键词：

MESENCHYMAL TRANSITION; PANCREATIC ADENOCARCINOMA; TYROSINE KINASE; LUNG-CANCER; SENSITIVITY; AMPLIFICATION; PROGRESSION; ACTIVATION; BIOLOGY; GENOME;

D O I：

10.1016/j.ccr.2009.03.022

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

K-ras mutations occur frequently in epithelial cancers. Using short hairpin RNAs to deplete K-Ras in lung and pancreatic cancer cell lines harboring K-ras mutations, two classes were identified-lines that do or do not require K-Ras to maintain viability. Comparing these two classes of cancer cells revealed a gene expression signature in K-Ras-dependent cells, associated with a well-differentiated epithelial phenotype, which was also seen in primary tumors. Several of these genes encode pharmacologically tractable proteins, such as Syk and Ron kinases. and integrin beta 6, depletion of which induces epithelial-mesenchymal transformation (EMT) and apoptosis specifically in K-Ras-dependent cells. These findings indicate that epithelial differentiation and tumor cell viability are associated, and that EMT regulators in "K-Ras-addicted" cancers represent candidate therapeutic targets.

引用

页码：489 / 500

页数：12

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