| First Author | Quach C | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 5681 |
| PubMed ID | 31831743 | Mgi Jnum | J:286814 |
| Mgi Id | MGI:6388351 | Doi | 10.1038/s41467-019-13475-w |
| Citation | Quach C, et al. (2019) A truncating mutation in the autophagy gene UVRAG drives inflammation and tumorigenesis in mice. Nat Commun 10(1):5681 |
| abstractText | Aberrant autophagy is a major risk factor for inflammatory diseases and cancer. However, the genetic basis and underlying mechanisms are less established. UVRAG is a tumor suppressor candidate involved in autophagy, which is truncated in cancers by a frameshift (FS) mutation and expressed as a shortened UVRAG(FS). To investigate the role of UVRAG(FS) in vivo, we generated mutant mice that inducibly express UVRAG(FS) (iUVRAG(FS)). These mice are normal in basal autophagy but deficient in starvation- and LPS-induced autophagy by disruption of the UVRAG-autophagy complex. iUVRAG(FS) mice display increased inflammatory response in sepsis, intestinal colitis, and colitis-associated cancer development through NLRP3-inflammasome hyperactivation. Moreover, iUVRAG(FS) mice show enhanced spontaneous tumorigenesis related to age-related autophagy suppression, resultant beta-catenin stabilization, and centrosome amplification. Thus, UVRAG is a crucial autophagy regulator in vivo, and autophagy promotion may help prevent/treat inflammatory disease and cancer in susceptible individuals. |
