| http://purl.uniprot.org/citations/35508175 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35508175 | http://www.w3.org/2000/01/rdf-schema#comment | "Pancreatic ductal adenocarcinoma (PDA) cells reprogram their transcriptional and metabolic programs to survive the nutrient-poor tumor microenvironment. Through in vivo CRISPR screening, we discovered islet-2 (ISL2) as a candidate tumor suppressor that modulates aggressive PDA growth. Notably, ISL2, a nuclear and chromatin-associated transcription factor, is epigenetically silenced in PDA tumors and high promoter DNA methylation or its reduced expression correlates with poor patient survival. The exogenous ISL2 expression or CRISPR-mediated upregulation of the endogenous loci reduces cell proliferation. Mechanistically, ISL2 regulates the expression of metabolic genes, and its depletion increases oxidative phosphorylation (OXPHOS). As such, ISL2-depleted human PDA cells are sensitive to the inhibitors of mitochondrial complex I in vitro and in vivo. Spatial transcriptomic analysis shows heterogeneous intratumoral ISL2 expression, which correlates with the expression of critical metabolic genes. These findings nominate ISL2 as a putative tumor suppressor whose inactivation leads to increased mitochondrial metabolism that may be exploitable therapeutically."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.devcel.2022.04.014"xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Yang J."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Bardeesy N."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Adli M."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Kuscu C."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Hwang W.L."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Hsu K.L."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Ware T.B."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Kashatus D.F."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Chandel N.S."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Cingoz H."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Kinali M."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Nagdas S."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Bauer T.W."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Ting D.T."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Adair S.J."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Luleyap H.U."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Ozturk H."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Comertpay G."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Tummala K.S."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Tufan T."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Bingul Y."xsd:string |
| http://purl.uniprot.org/citations/35508175 | http://purl.uniprot.org/core/author | "Goudreau B.J."xsd:string |