Matches in SemOpenAlex for { <https://semopenalex.org/work/W2885674756> ?p ?o ?g. }
Showing items 1 to 88 of
88
with 100 items per page.
- W2885674756 abstract "ARF6 is a member of the adenosine diphosphate (ADP)-ribosylation factor (ARF) family of small GTPases and is part of the RAS superfamily. We have shown that pharmacologic inhibition of ARF6 can inhibit proliferation of uveal melanoma and invasion/metastasis of cutaneous melanoma. Most cutaneous melanomas are defined by mutually-exclusive driver mutations in BRAF, NRAS, or NF1. These subtypes share similar mechanisms of oncogenesis because they align along a continuum of RAS signaling. Mutations in the PI3K pathway occur in a fraction of all melanoma subtypes, indicating a selective advantage for PI3K/AKT activation beyond BRAF or RAS activation. We and others have reported ARF6-dependent ERK activation occurring upon either extracellular ligand stimulation or mutant oncoprotein signaling. Recently, ARF6 has also been shown to be upstream of PI3K signaling. Based on these findings, we hypothesized that ARF6 is critical for both the RAF and PI3K arms of the RAS pathway and that loss of ARF6 will impede tumor growth driven by these oncogenes. We tested this hypothesis using human melanoma cell lines and with an inducible, genetically engineered mouse model (GEMM) of melanoma. Our data reveal that pharmacologic inhibition of ARF6 can reduce proliferation of BRAF, NRAS and NF1-mutated melanoma cells. Furthermore, loss of Arf6 causes a reduction in mean tumor size and improves survival in BRAFV600E/CDKN2ANULL/PTENNULL/AKTE17K and BRAFV600E/CDKN2ANULL/PTENNULL mice. These results indicate that ARF6 is necessary for melanomagenesis and for oncogenic BRAF and/or PI3K signaling. Our data suggest that ARF6 may be an actionable node in the RAS pathway and that therapeutic targeting of ARF6 has the potential to improve current treatment methods for progressive disease. Citation Format: Lehi Acosta, Aaron Rogers, Jingfu Peng, Alan Mueller, Zongzhong Tong, Donghan Shin, Jae Hyuk Yoo, Dean Y. Li, Shannon J. Odelberg, Sheri L. Holmen, Allie H. Grossmann. The small GTPase ARF6 is necessary for melanomagenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4367." @default.
- W2885674756 created "2018-08-22" @default.
- W2885674756 creator A5010156703 @default.
- W2885674756 creator A5016072013 @default.
- W2885674756 creator A5024714084 @default.
- W2885674756 creator A5029180727 @default.
- W2885674756 creator A5033315287 @default.
- W2885674756 creator A5045434227 @default.
- W2885674756 creator A5049683384 @default.
- W2885674756 creator A5057839133 @default.
- W2885674756 creator A5061736368 @default.
- W2885674756 creator A5065788456 @default.
- W2885674756 creator A5080990410 @default.
- W2885674756 date "2018-07-01" @default.
- W2885674756 modified "2023-09-25" @default.
- W2885674756 title "Abstract 4367: The small GTPase ARF6 is necessary for melanomagenesis" @default.
- W2885674756 doi "https://doi.org/10.1158/1538-7445.am2018-4367" @default.
- W2885674756 hasPublicationYear "2018" @default.
- W2885674756 type Work @default.
- W2885674756 sameAs 2885674756 @default.
- W2885674756 citedByCount "0" @default.
- W2885674756 crossrefType "proceedings-article" @default.
- W2885674756 hasAuthorship W2885674756A5010156703 @default.
- W2885674756 hasAuthorship W2885674756A5016072013 @default.
- W2885674756 hasAuthorship W2885674756A5024714084 @default.
- W2885674756 hasAuthorship W2885674756A5029180727 @default.
- W2885674756 hasAuthorship W2885674756A5033315287 @default.
- W2885674756 hasAuthorship W2885674756A5045434227 @default.
- W2885674756 hasAuthorship W2885674756A5049683384 @default.
- W2885674756 hasAuthorship W2885674756A5057839133 @default.
- W2885674756 hasAuthorship W2885674756A5061736368 @default.
- W2885674756 hasAuthorship W2885674756A5065788456 @default.
- W2885674756 hasAuthorship W2885674756A5080990410 @default.
- W2885674756 hasConcept C104317684 @default.
- W2885674756 hasConcept C1167327 @default.
- W2885674756 hasConcept C121608353 @default.
- W2885674756 hasConcept C163181125 @default.
- W2885674756 hasConcept C207332259 @default.
- W2885674756 hasConcept C21790070 @default.
- W2885674756 hasConcept C2777658100 @default.
- W2885674756 hasConcept C2781187634 @default.
- W2885674756 hasConcept C501734568 @default.
- W2885674756 hasConcept C502942594 @default.
- W2885674756 hasConcept C54355233 @default.
- W2885674756 hasConcept C555283112 @default.
- W2885674756 hasConcept C57074206 @default.
- W2885674756 hasConcept C62478195 @default.
- W2885674756 hasConcept C75217442 @default.
- W2885674756 hasConcept C80631254 @default.
- W2885674756 hasConcept C86554907 @default.
- W2885674756 hasConcept C86803240 @default.
- W2885674756 hasConcept C95444343 @default.
- W2885674756 hasConceptScore W2885674756C104317684 @default.
- W2885674756 hasConceptScore W2885674756C1167327 @default.
- W2885674756 hasConceptScore W2885674756C121608353 @default.
- W2885674756 hasConceptScore W2885674756C163181125 @default.
- W2885674756 hasConceptScore W2885674756C207332259 @default.
- W2885674756 hasConceptScore W2885674756C21790070 @default.
- W2885674756 hasConceptScore W2885674756C2777658100 @default.
- W2885674756 hasConceptScore W2885674756C2781187634 @default.
- W2885674756 hasConceptScore W2885674756C501734568 @default.
- W2885674756 hasConceptScore W2885674756C502942594 @default.
- W2885674756 hasConceptScore W2885674756C54355233 @default.
- W2885674756 hasConceptScore W2885674756C555283112 @default.
- W2885674756 hasConceptScore W2885674756C57074206 @default.
- W2885674756 hasConceptScore W2885674756C62478195 @default.
- W2885674756 hasConceptScore W2885674756C75217442 @default.
- W2885674756 hasConceptScore W2885674756C80631254 @default.
- W2885674756 hasConceptScore W2885674756C86554907 @default.
- W2885674756 hasConceptScore W2885674756C86803240 @default.
- W2885674756 hasConceptScore W2885674756C95444343 @default.
- W2885674756 hasLocation W28856747561 @default.
- W2885674756 hasOpenAccess W2885674756 @default.
- W2885674756 hasPrimaryLocation W28856747561 @default.
- W2885674756 hasRelatedWork W2035816919 @default.
- W2885674756 hasRelatedWork W2049468996 @default.
- W2885674756 hasRelatedWork W2138401670 @default.
- W2885674756 hasRelatedWork W2141202463 @default.
- W2885674756 hasRelatedWork W2164992866 @default.
- W2885674756 hasRelatedWork W2884425950 @default.
- W2885674756 hasRelatedWork W2885674756 @default.
- W2885674756 hasRelatedWork W2886820740 @default.
- W2885674756 hasRelatedWork W2890752806 @default.
- W2885674756 hasRelatedWork W3129743340 @default.
- W2885674756 isParatext "false" @default.
- W2885674756 isRetracted "false" @default.
- W2885674756 magId "2885674756" @default.
- W2885674756 workType "article" @default.