Letter
KRAS Activating Signaling Triggers Arteriovenous Malformations

https://doi.org/10.1016/j.tibs.2018.04.007Get rights and content

The underlying genetic causes and altered signaling pathways of brain arteriovenous malformations remain unknown. A study published in The New England Journal of Medicine reported that KRAS somatic mutations (p.Gly12Val/Asp) were identified in brain arteriovenous malformations of human subjects and endothelial cell-enriched cultures, which might specifically activate the MAPK (mitogen-activated protein kinase)–ERK (extracellular signal-regulated kinase) signaling pathway in brain endothelial cells.

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Acknowledgments

This work was supported by K99HL138272 from NHLBI. This work has been funded in whole or in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN261200800001E to R.N.

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Cited by (12)

  • A human model of arteriovenous malformation (AVM)-on-a-chip reproduces key disease hallmarks and enables drug testing in perfused human vessel networks

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    The inability of a MEKi to reduce vessel size in AVM-on-a-chip vessels suggests that other cell types or signaling pathways may be affected by KRAS activation in ECs [44]. KRAS is one of the most frequently mutated oncogenes in cancer and plays a central role in several growth factor receptor tyrosine kinase signaling pathways [7,8,59,60]. As a result, targeting the MAPK/ERK and KRAS protein activity for cancer treatment is of high interest.

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