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您的检索式：作者名="Peter J.Nelson"
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| 1 | Insulin-like growth factor 1-induced enolase 2 deacetylation by HDAC3 promotes metastasis of pancreatic cancer显示文摘Enolase 2(ENO2)is a key glycolytic enzyme in the metabolic process of glycolysis,but its potential function in pancreatic ductal adenocarcinoma(PDAC)is unclear.In this study,we observed a significant overexpression of ENO2 in PDAC tissues,and its expression was correlated with metastasis and poor prognosis in PDAC patients.K394 was identified as a major acetylation site in ENO2 that regulates its enzymatic activity,cell metabolism and PDAC progression.Knockdown of ENO2 suppressed tumor growth and liver metastasis in PDAC.Re-expression of wild-type(WT)ENO2,but not the K394 acetylation mimetic mutant,could reverse the decreased tumor malignancy.We further characterized histone deacetylase 3(HDAC3)and P300/CBP-associated factor(PCAF)as the potential deacetylase and acetyltransferase for ENO2,respectively.HDAC3-mediated deacetylation was shown to lead to ENO2 activation and enhancement of glycolysis.Importantly,insulin-like growth factor-1(IGF-1)was found to decrease K394 acetylation and stimulate ENO2 activity in a dose-and time-dependent manner.The PI3K/AKT/mTOR pathway facilitated the phosphorylation of HDAC3 on S424,which promoted K394 deacetylation and activation of ENO2.Linsitinib,an oral small-molecule inhibitor of IGF-1R,could inhibit IGF-1-induced ENO2 deacetylation by HDAC3 and the PI3K/AKT/mTOR pathway.Furthermore,linsitinib showed a different effect on the growth and metastasis of PDAC depending on the overexpression of WT versus K394-mutant ENO2.Our results reveal a novel mechanism by which acetylation negatively regulates ENO2 activity in the metastasis of PDAC by modulating glycolysis.Blockade of IGF-1-induced ENO2 deacetylation represents a promising strategy to prevent the development of PDAC. | Yan Zheng Chao Wu Jimeng Yang Yue Zhao Huliang Jia Min Xue Da Xu Feng Yang Deliang Fu Chaoqun Wang Beiyuan Hu Ze Zhang Tianen Li Shican Yan Xuan Wang Peter J.Nelson Christiane Bruns Lunxiu Qin Qiongzhu Dong | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 3 |
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