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Publication : A gene expression signature associated with "K-Ras addiction" reveals regulators of EMT and tumor cell survival.

First Author  Singh A Year  2009
Journal  Cancer Cell Volume  15
Issue  6 Pages  489-500
PubMed ID  19477428 Mgi Jnum  J:149663
Mgi Id  MGI:3848841 Doi  10.1016/j.ccr.2009.03.022
Citation  Singh A, et al. (2009) A gene expression signature associated with 'K-Ras addiction' reveals regulators of EMT and tumor cell survival. Cancer Cell 15(6):489-500
abstractText  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 beta6, 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.
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