期刊
CELL DEATH AND DIFFERENTIATION
卷 30, 期 2, 页码 313-326出版社
SPRINGERNATURE
DOI: 10.1038/s41418-022-01063-3
关键词
-
This study found that SIRT4 activates the phosphorylation of p53 protein and promotes autophagy in PDAC by suppressing glutamine metabolism, thereby inhibiting tumor growth and progression.
The role of autophagy in cancer is context-dependent. In the present study, we aimed to investigate the regulator and underlying mechanism of autophagy. We found that a sirtuin (SIRT) family member, SIRT4, was significantly associated autophagy pathway in pancreatic ductal adenocarcinoma (PDAC). Specifically, in vitro cell culture experiments and in vivo transgenic and xenografted animal models revealed that SIRT4 could inhibit tumor growth and promote autophagy in PDAC. In terms of the mechanism, we demonstrated that SIRT4 activated the phosphorylation of p53 protein by suppressing glutamine metabolism, which was crucial in SIRT4-induced autophagy. AMPK alpha was implicated in the regulation of autophagy and phosphorylation of p53 mediated by SIRT4, contributing to the suppression of pancreatic tumorigenesis. Notably, the clinical significance of the SIRT4/AMPK alpha/p53/autophagy axis was demonstrated in human PDAC specimens. Collectively, these findings suggested that SIRT4-induced autophagy further inhibited tumorigenesis and progression of PDAC, highlighting the potential of SIRT4 as a therapeutic target for cancer.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据