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Learn MoreWe analyzed transcriptomes from BRAFV600E/CDKN2ANull + ARF6Q67L mouse melanoma tumors to identify novel ARF6-regulated target genes and pathways. A unique gene expression signature in the ARF6Q67L tumors included upregulated genes related to known ARF6-dependent cell functions in trafficking, cell adhesion, motility, providing an internal positive control that helps to validate the utility of RNA sequencing as a discovery tool for ARF6. Interestingly, mTOR signaling components were upregulated in ARF6Q67L tumors, including Pik3r1, which encodes the p85 regulatory subunit of PI3 kinase (PI3K). This finding is provocative because the PI3K pathway is strongly linked to melanoma disease progression and because our ARF6Q67L mice showed a comparable metastatic phenotype to mice with PTEN loss. Transcript levels of Pik3r1 were increased in ARF6Q67L tumors compared to BrafCA;Cdkn2af/f controls. SOURCE: Chris Stubben Huntsman Cancer Institute
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