| First Author | Postler TS | Year | 2023 |
| Journal | Proc Natl Acad Sci U S A | Volume | 120 |
| Issue | 46 | Pages | e2312595120 |
| PubMed ID | 37931099 | Mgi Jnum | J:347981 |
| Mgi Id | MGI:7639618 | Doi | 10.1073/pnas.2312595120 |
| Citation | Postler TS, et al. (2023) A pan-cancer analysis implicates human NKIRAS1 as a tumor-suppressor gene. Proc Natl Acad Sci U S A 120(46):e2312595120 |
| abstractText | The NF-kappaB family of transcription factors and the Ras family of small GTPases are important mediators of proproliferative signaling that drives tumorigenesis and carcinogenesis. The kappaB-Ras proteins were previously shown to inhibit both NF-kappaB 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 kappaB-Ras proteins for tumorigenesis. Additionally, we have utilized a pan-cancer bioinformatics analysis to explore the role of the kappaB-Ras proteins in human cancers. Surprisingly, we find that the genes encoding kappaB-Ras 1 (NKIRAS1) and kappaB-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. |
