Critical role for transcriptional repressor Snail2 in transformation by oncogenic RAS in colorectal carcinoma cells

被引：88

作者：

Wang, Y. ^{[1
]}

Ngo, V. N. ^{[2
]}

Marani, M. ^{[1
]}

Yang, Y. ^{[2
]}

Wright, G. ^{[3
]}

Staudt, L. M. ^{[2
]}

Downward, J. ^{[1
]}

机构：

[1] Canc Res UK London Res Inst, Signal Transduct Lab, London WC2A 3PX, England

[2] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[3] NCI, Biometr Res Branch, DCTD, NIH, Bethesda, MD 20892 USA

来源：

ONCOGENE | 2010年 / 29卷 / 33期

关键词：

KRAS; synthetic lethal; oncogene addiction; epithelial-mesenchymal transition; EPITHELIAL-MESENCHYMAL TRANSITIONS; E-CADHERIN EXPRESSION; RNA INTERFERENCE; P53-MEDIATED APOPTOSIS; TUMOR PROGRESSION; CANCER-CELLS; FACTOR SLUG; LINES; GROWTH; GENE;

D O I：

10.1038/onc.2010.218

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Activating mutations in the KRAS gene are among the most prevalent genetic changes in human cancers. To identify synthetic lethal interactions in cancer cells harbouring mutant KRAS, we performed a large-scale screen in isogenic paired colon cancer cell lines that differ by a single allele of mutant KRAS using an inducible short hairpin RNA interference library. Snail2, a zinc finger transcriptional repressor encoded by the SNAI2 gene, was found to be selectively required for the long-term survival of cancer cells with mutant KRAS that have undergone epithelial-mesenchymal transition (EMT), a transdifferentiation event that is frequently seen in advanced tumours and is promoted by RAS activation. Snail2 expression is regulated by the RAS pathway and is required for EMT. Our findings support Snail2 as a possible target for the treatment of the broad spectrum of human cancers of epithelial origin with mutant RAS that have undergone EMT and are characterized by a high degree of chemoresistance and radioresistance. Oncogene (2010) 29, 4658-4670; doi:10.1038/onc.2010.218; published online 21 June 2010

引用

页码：4658 / 4670

页数：13