Show simple item record

dc.contributor.authorCiavattone, N.
dc.contributor.authorYounis, R.
dc.contributor.authorWang, L.
dc.contributor.authorZhang, Y.
dc.contributor.authorDavila, E.
dc.date.accessioned2020-06-24T20:50:55Z
dc.date.available2020-06-24T20:50:55Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85086330329&doi=10.1038%2fs42003-020-1033-y&partnerID=40&md5=43b395cd8f051be614e1069bccba796d
dc.identifier.urihttp://hdl.handle.net/10713/13121
dc.description.abstractMelanoma represents the most serious type of skin cancer. Although recent years have seen advances using targeted and immunotherapies, most patients remain at high risk for tumor recurrence. Here we show that IRAK-M, a negative regulator of MyD88 signaling, is deficient or low in melanoma and expression levels correlate with patient survival. Inducing IRAK-M expression using genetic approaches or epigenetic modifiers initiates apoptosis by prompting its interaction with TRAF6 via IRAK-M's C-terminal domain. This complex recruits and degrades calpastatin which stimulates calpain activity and triggers caspase-3-dependent but caspase-8,-9-independent apoptosis. Using a drug screen, we identified compounds that induced IRAK-M expression. Administration of IRAK-M-inducing drugs reduced tumor growth in mice but was ineffective against IRAK-M knock-down tumors. These results uncover a previously uncharacterized apoptosis pathway, emphasize IRAK-M as a potential therapeutic target and suggest that the anticancer activity of certain drugs could do so through their ability to induce IRAK-M expression. Copyright 2020, The Author(s).en_US
dc.description.sponsorshipThis work was supported by the US Department of Veteran Affair Merit Award 1I01BX002142, National Cancer Institute R01CA207913, the University of Maryland Greenebaum Comprehensive Cancer Center, and the University of Colorado Comprehensive Cancer Center.en_US
dc.description.urihttps://doi.org/10.1038/s42003-020-1033-yen_US
dc.language.isoen_USen_US
dc.publisherNature Researchen_US
dc.relation.ispartofCommunications Biology
dc.subjectIRAK-M expressionen_US
dc.subjectcalpastatinen_US
dc.subject.meshMelanomaen_US
dc.subject.meshApoptosisen_US
dc.subject.meshTNF Receptor-Associated Factor 6en_US
dc.titleInduction of IRAK-M in melanoma induces caspase-3 dependent apoptosis by reducing TRAF6 and calpastatin levelsen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s42003-020-1033-y
dc.identifier.pmid32533049


This item appears in the following Collection(s)

Show simple item record