Title: UVRAG in autophagy, inflammation, and cancer.
Authors: Song, Ying; Quach, Christine; Liang, Chengyu
Published In Autophagy, (2020 02)
Abstract: Macroautophagy/autophagy deregulation has been observed in perpetuated inflammation and the proliferation of tumor cells. However, the mechanisms underlying these changes have yet to be well-identified. UVRAG is one of the key players of autophagy, but its role in vivo remained puzzling. Our recent study utilized a mouse model with inducible expression of a cancer-derived frameshift (FS) mutation in UVRAG that dominant-negatively inhibits wild-type UVRAG, resulting in impaired stimulus-induced autophagy. The systemically compromised autophagy, particularly mitophagy, notably increases inflammation and associated pathologies. Furthermore, our discovery indicates that time-dependent autophagy suppression and ensuing CTNNB1/β-catenin activation may serve as one tumor-promoting mechanism underpinning age-related cancer susceptibility.
PubMed ID: 31905312
MeSH Terms: Animals; Autophagosomes/metabolism; Autophagy*; Frameshift Mutation/genetics; Inflammation/metabolism*; Inflammation/pathology*; Mice; Neoplasms/metabolism*; Neoplasms/pathology*; Signal Transduction; Tumor Suppressor Proteins/genetics; Tumor Suppressor Proteins/metabolism*