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Ref Type Journal Article
PMID (19477428)
Authors Singh A, Greninger P, Rhodes D, Koopman L, Violette S, Bardeesy N, Settleman J
Title A gene expression signature associated with "K-Ras addiction" reveals regulators of EMT and tumor cell survival.
Journal Vol Issue Date Pages Journal Short Title
Cancer cell 15 6 2009 Jun 2 489-500 Cancer Cell
URL
Abstract Text 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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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References