Oncogene Signaling

KRAS gets the silencing treatment

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Science  04 Mar 2016:
Vol. 351, Issue 6277, pp. 1039-1040
DOI: 10.1126/science.351.6277.1039-e

Mutations in the KRAS protooncogene drive the growth of some of the most lethal human tumors, including pancreatic and lung cancers. Efforts to pharmacologically inhibit KRAS itself, or components of its well-studied signaling pathway, have been largely unsuccessful. Shankar et al. considered the possibility that KRAS may have additional uncharacterized roles that contribute to tumor development and that may be more susceptible to drug treatment. They explored this idea by using a sensitive method to identify new KRAS-binding proteins. One surprising hit was Argonaute 2 (AGO2), a protein required for RNA-mediated gene silencing. KRAS and AGO2 colocalize in the endoplasmic reticulum and their interaction alters the activity of each protein. Notably, AGO2 appears to enhance the transforming ability of KRAS in cultured cells.

Cell Rep. 14, 1 (2016).

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