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dc.contributor.authorFisher, M.L.
dc.contributor.authorGrun, D.
dc.contributor.authorAdhikary, G.
dc.date.accessioned2019-11-01T12:49:34Z
dc.date.available2019-11-01T12:49:34Z
dc.date.issued2017
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85038077584&doi=10.18632%2foncotarget.22628&partnerID=40&md5=911318988267d620d02950eea73fed29
dc.identifier.urihttp://hdl.handle.net/10713/11275
dc.description.abstractTreating BRAF inhibitor-resistant melanoma is an important therapeutic goal. Thus, it is important to identify and target mechanisms of resistance to improve therapy. The YAP1 and TAZ proteins of the Hippo signaling pathway are important drivers of cancer cell survival, and are BRAF inhibitor resistant factors in melanoma. We examine the role of YAP1/TAZ in melanoma cancer stem cells (MCS cells). We demonstrate that YAP1, TAZ and TEAD (TEA domain transcription factor) levels are elevated in BRAF inhibitor resistant MCS cells and enhance cell survival, spheroid formation, matrigel invasion and tumor formation. Moreover, increased YAP1, TAZ and TEAD are associated with sustained ERK1/2 activity that is not suppressed by BRAF inhibitor. Xenograft studies show that treating BRAF inhibitor-resistant tumors with verteporfin, an agent that interferes with YAP1 function, reduces YAP1/TAZ level, restores BRAF inhibitor suppression of ERK1/2 signaling and reduces tumor growth. Verteporfin is highly effective as concentrations of verteporfin that do not impact tumor formation restore BRAF inhibitor suppression of tumor formation, suggesting that co-treatment with agents that inhibit YAP1 and BRAF(V600E) may be a viable therapy for cancer stem cell-derived BRAF inhibitor-resistant melanoma. Copyright 2017 2017 Fisher et al.en_US
dc.description.sponsorshipThis work was supported by National Institutes of Health grants R01-CA184027 and R01-CA131074 to Richard Eckert.en_US
dc.description.urihttps://doi.org/10.18632/oncotarget.22628en_US
dc.language.isoen_USen_US
dc.publisherImpact Journals LLCen_US
dc.relation.ispartofOncotarget
dc.subjectBRAF inhibitoren_US
dc.subjectCancer stem cellen_US
dc.subjectDrug resistanceen_US
dc.subjectMelanomaen_US
dc.subjectYAP and TAZen_US
dc.titleInhibition of YAP function overcomes BRAF inhibitor resistance in melanoma cancer stem cellsen_US
dc.typeArticleen_US
dc.identifier.doi10.18632/oncotarget.22628


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