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- W2912978179 abstract "Abstract Caspase-2 is a highly conserved cysteine protease with roles in apoptosis and tumor suppression. Our recent findings have also demonstrated that the tumor suppression function of caspase-2 is context specific. In particular, while caspase-2 deficiency augments lymphoma development in the EμMyc mouse model, it leads to delayed neuroblastoma development in Th-MYCN mice. However, it is unclear how caspase-2 mediates these differential outcomes. Here we utilized RNA sequencing to define the transcriptomic changes caused by caspase-2 ( Casp2 −/− ) deficiency in tumors from EμMyc and Th-MYCN mice. We describe key changes in both lymphoma and neuroblastoma-associated genes and identified differential expression of the EGF-like domain-containing gene, Megf6 , in the two tumor types that may contribute to tumor outcome following loss of Casp2 . We identified a panel of genes with altered expression in Th-MYCN/Casp2 −/− tumors that are strongly associated with neuroblastoma outcome, with roles in melanogenesis, Wnt and Hippo pathway signaling, that also contribute to neuronal differentiation. In contrast, we found that key changes in gene expression in the EμMyc/Casp2 −/− tumors, are associated with increased immune signaling and T-cell infiltration previously associated with more aggressive lymphoma progression. In addition, Rap1 signaling pathway was uniquely enriched in Casp2 deficient EμMyc tumors. Our findings suggest that Casp2 deficiency augments immune signaling pathways that may be in turn, enhance lymphomagenesis. Overall, our study has identified new genes and pathways that contribute to the caspase-2 tumor suppressor function and highlight distinct roles for caspase-2 in different tissues." @default.
- W2912978179 created "2019-02-21" @default.
- W2912978179 creator A5011765291 @default.
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- W2912978179 creator A5072009574 @default.
- W2912978179 date "2019-01-22" @default.
- W2912978179 modified "2023-10-18" @default.
- W2912978179 title "Transcriptome profiling of caspase-2 deficient EμMyc and Th-MYCN mouse tumors identifies distinct putative roles for caspase-2 in neuronal differentiation and immune signaling" @default.
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- W2912978179 doi "https://doi.org/10.1038/s41419-018-1296-0" @default.
- W2912978179 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6343006" @default.
- W2912978179 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30670683" @default.
- W2912978179 hasPublicationYear "2019" @default.
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