UVRAG in autophagy, inflammation, and cancer.
UVRAG in autophagy, inflammation, and cancer.
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UVRAG 在自噬、炎症和癌症中的作用。
DOI：
10.1080/15548627.2019.1709768
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发表时间：
2020
期刊：
影响因子：
13.3
通讯作者：
Liang,Chengyu
中科院分区：
文献类型：
--
作者：
Song,Ying;Quach,Christine;Liang,Chengyu
已经在永久性炎症和肿瘤细胞增殖中观察到大自噬/自噬失调。然而，这些变化背后的机制尚未得到很好的确定。UVRAG是自噬的关键参与者之一，但其在体内的作用仍然令人困惑。我们最近的研究利用了一种小鼠模型，该模型具有UVRAG中癌症衍生的移码（FS）突变的诱导表达，该突变显性负抑制野生型UVRAG，导致刺激诱导的自噬受损。系统性受损的自噬，特别是线粒体自噬，显著增加炎症和相关的病理。此外，我们的发现表明，时间依赖性自噬抑制和随后的CTNNB 1/β-catenin激活可能是一种支持年龄相关癌症易感性的肿瘤促进机制。
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 inUVRAGthat 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.