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A pan-cancer analysis implicates human NKIRAS1 as a tumor-suppressor gene.
Postler, Thomas S; Wang, Anqi; Brundu, Francesco G; Wang, Pingzhang; Wu, Zikai; Butler, Kelly E; Grinberg-Bleyer, Yenkel; Krishnareddy, Suneeta; Lagana, Stephen M; Saqi, Anjali; Oeckinghaus, Andrea; Rabadan, Raul; Ghosh, Sankar.
Afiliação
  • Postler TS; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032.
  • Wang A; Program for Mathematical Genomics, Department of Systems Biology, Columbia University, New York, NY 10032.
  • Brundu FG; Department of Biomedical Informatics, Columbia University, New York, NY 10032.
  • Wang P; Program for Mathematical Genomics, Department of Systems Biology, Columbia University, New York, NY 10032.
  • Wu Z; Department of Biomedical Informatics, Columbia University, New York, NY 10032.
  • Butler KE; Program for Mathematical Genomics, Department of Systems Biology, Columbia University, New York, NY 10032.
  • Grinberg-Bleyer Y; Department of Biomedical Informatics, Columbia University, New York, NY 10032.
  • Krishnareddy S; Program for Mathematical Genomics, Department of Systems Biology, Columbia University, New York, NY 10032.
  • Lagana SM; Department of Biomedical Informatics, Columbia University, New York, NY 10032.
  • Saqi A; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032.
  • Oeckinghaus A; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032.
  • Rabadan R; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032.
  • Ghosh S; Division of Digestive and Liver Diseases, Department of Medicine, College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032.
Proc Natl Acad Sci U S A ; 120(46): e2312595120, 2023 Nov 14.
Article em En | MEDLINE | ID: mdl-37931099
The NF-κB family of transcription factors and the Ras family of small GTPases are important mediators of proproliferative signaling that drives tumorigenesis and carcinogenesis. The κB-Ras proteins were previously shown to inhibit both NF-κB and Ras activation through independent mechanisms, implicating them as tumor suppressors with potentially broad relevance to human cancers. In this study, we have used two mouse models to establish the relevance of the κB-Ras proteins for tumorigenesis. Additionally, we have utilized a pan-cancer bioinformatics analysis to explore the role of the κB-Ras proteins in human cancers. Surprisingly, we find that the genes encoding κB-Ras 1 (NKIRAS1) and κB-Ras 2 (NKIRAS2) are rarely down-regulated in tumor samples with oncogenic Ras mutations. Reduced expression of human NKIRAS1 alone is associated with worse prognosis in at least four cancer types and linked to a network of genes implicated in tumorigenesis. Our findings provide direct evidence that loss of NKIRAS1 in human tumors that do not carry oncogenic RAS mutations is associated with worse clinical outcomes.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas de Transporte / Genes Supressores de Tumor / Carcinogênese Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas de Transporte / Genes Supressores de Tumor / Carcinogênese Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article