| First Author | Nopparat J | Year | 2015 |
| Journal | Oncogene | Volume | 34 |
| Issue | 12 | Pages | 1542-52 |
| PubMed ID | 24727894 | Mgi Jnum | J:221282 |
| Mgi Id | MGI:5638828 | Doi | 10.1038/onc.2014.89 |
| Citation | Nopparat J, et al. (2015) delta-Catenin, a Wnt/beta-catenin modulator, reveals inducible mutagenesis promoting cancer cell survival adaptation and metabolic reprogramming. Oncogene 34(12):1542-52 |
| abstractText | Mutations of Wnt/beta-catenin signaling pathway has essential roles in development and cancer. Although beta-catenin and adenomatous polyposis coli (APC) gene mutations are well established and are known to drive tumorigenesis, discoveries of mutations in other components of the pathway lagged, which hinders the understanding of cancer mechanisms. Here we report that delta-catenin (gene designation: CTNND2), a primarily neural member of the beta-catenin superfamily that promotes canonical Wnt/beta-catenin/LEF-1-mediated transcription, displays exonic mutations in human prostate cancer and promotes cancer cell survival adaptation and metabolic reprogramming. When overexpressed in cells derived from prostate tumor xenografts, delta-catenin gene invariably gives rise to mutations, leading to sequence disruptions predicting functional alterations. Ectopic delta-catenin gene integrating into host chromosomes is locus nonselective. delta-Catenin mutations promote tumor development in mouse prostate with probasin promoter (ARR2PB)-driven, prostate-specific expression of Myc oncogene, whereas mutant cells empower survival advantage upon overgrowth and glucose deprivation. Reprogramming energy utilization accompanies the downregulation of glucose transporter-1 and poly (ADP-ribose) polymerase cleavage while preserving tumor type 2 pyruvate kinase expression. delta-Catenin mutations increase beta-catenin translocation to the nucleus and hypoxia-inducible factor 1alpha (HIF-1alpha) expression. Therefore, introducing delta-catenin mutations is an important milestone in prostate cancer metabolic adaptation by modulating beta-catenin and HIF-1alpha signaling under glucose shortage to amplify its tumor-promoting potential. |
