April 28, 2016

An Argonaute’s voyage to cancer

A genetic mutation that promotes cancer development blocks the normal sorting of a protein called “Argonaute 2.”

Mutations in the KRAS gene, which codes for a protein involved in normal cell signaling, promote the development of colorectal and other cancers.

One mechanism by which activated KRAS may influence the phenotype of neighboring cells is by regulating the packaging of tiny RNAs called microRNAs (miRNAs) in small, bubble-like vesicles called exosomes.

When delivered to surrounding cells, miRNAs can affect the translation of messenger RNA in ways that promote or inhibit cancer growth and metastasis.

Vanderbilt University researchers have found a potential clue to how this is done through spatiotemporal regulation of Argonaute 2 (Ago2), a component of the RNA-induced silencing complex that can degrade messenger RNA.

In Cell Reports, Alissa Weaver, M.D. Ph.D., Andrew McKenzie, Ph.D., and colleagues describe how overactivity of KRAS due to mutation inhibits normal sorting of Ago2 into exosomes.

Inhibition of the enzyme MEK reverses this effect and leads to increased exosomal secretion of Ago2. The findings underscore the important roles miRNAs and exosomes play in cancer.

This research was supported by grants from the National Institutes of Health (CA179514, CA163563, CA095103).

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