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6-Phosphogluconate dehydrogenase promotes glycolysis and fatty acid synthesis by inhibiting the AMPK pathway in lung adenocarcinoma cells

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资源类型：
Pubmed体系：
作者：
Wu Jun[1,3,7] ; Chen Yong[4] ; Zou Hui[2,3] ; Xu Kaiyue[5] ; Hou Jiaqi[6] ; Wang Mengmeng[6] ; Tian Shuyu[6] ; Gao Mingjun[6] ; Ren Qinglin[6] ; Sun Chao[3] ; Lu Shichun[3] ; Wang Qiang[8] ; Shu Yusheng[2,3,7,*3] ; Wang Shouyu[8,*2] ; Wang Xiaolin[1,3,7,*1] ;
机构： [1]Medical College, Yangzhou University, Yangzhou, China [2]The Yangzhou School of Clinical Medicine of Nanjing Medical University, Yangzhou, China [3]Department of Thoracic Surgery, Northern Jiangsu People’s Hospital, Yangzhou, China [4]Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China [5]Department of Radiation Oncology, Suzhou Municipal Hospital, Suzhou, China [6]First College of Clinical Medicine, Dalian Medical University, Dalian, China [7]Yangzhou Key Laboratory of Thoracic and Cardiac Surgery, Yangzhou, China [8]Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Anhui Provincial Innovation Institute for Pharmaceutical Basic Research, Innovative Institute of Tumor Immunity and Medicine (ITIM), Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy, Hefei, China
出处：
DOI： 10.1016/j.canlet.2024.217177
ISSN：

关键词： Lung adenocarcinoma Single-cell sequencing Pentose phosphate pathway 6-Phosphogluconate dehydrogenase AMPK pathway

摘要：
Abnormal metabolism has emerged as a prominent hallmark of cancer and plays a pivotal role in carcinogenesis and progression of lung adenocarcinoma (LUAD). In this study, single-cell sequencing revealed that the metabolic enzyme 6-phosphogluconate dehydrogenase (PGD), which is a critical regulator of the pentose phosphate pathway (PPP), is significantly upregulated in the malignant epithelial cell subpopulation during malignant progression. However, the precise functional significance of PGD in LUAD and its underlying mechanisms remain elusive. Through the integration of TCGA database analysis and LUAD tissue microarray data, it was found that PGD expression was significantly upregulated in LUAD and closely correlated with a poor prognosis in LUAD patients. Moreover, in vitro and in vivo analyses demonstrated that PGD knockout and inhibition of its activity mitigated the proliferation, migration, and invasion of LUAD cells. Mechanistically, immunoprecipitation-mass spectrometry (IP-MS) revealed for the first time that IQGAP1 is a robust novel interacting protein of PGD. PGD decreased p-AMPK levels by competitively interacting with the IQ domain of the known AMPKα binding partner IQGAP1, which promoted glycolysis and fatty acid synthesis in LUAD cells. Furthermore, we demonstrated that the combination of Physcion (a PGD-specific inhibitor) and metformin (an AMPK agonist) could inhibit tumor growth more effectively both in vivo and in vitro. Collectively, these findings suggest that PGD is a potential prognostic biomarker and therapeutic target for LUAD.Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.

基金：
This study was supported by the Jiangsu Provincial Health Commission Research Project on Elderly Health (LKZ2022019), Yangzhou Social Development and Clinical Frontier Technology Project (YZ2023084), Yangzhou Innovation Capability Building Design Plan Project (YZ2022168) and Yangzhou Social Development and Clinical Frontier Technology Project (YZ2021078).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 1 区 医学
小类 | 2 区 肿瘤学
最新[2023]版：
大类 | 1 区 医学
小类 | 2 区 肿瘤学
第一作者：
第一作者机构： [1]Medical College, Yangzhou University, Yangzhou, China [3]Department of Thoracic Surgery, Northern Jiangsu People’s Hospital, Yangzhou, China [7]Yangzhou Key Laboratory of Thoracic and Cardiac Surgery, Yangzhou, China
共同第一作者：
通讯作者：
通讯机构： [1]Medical College, Yangzhou University, Yangzhou, China [2]The Yangzhou School of Clinical Medicine of Nanjing Medical University, Yangzhou, China [3]Department of Thoracic Surgery, Northern Jiangsu People’s Hospital, Yangzhou, China [7]Yangzhou Key Laboratory of Thoracic and Cardiac Surgery, Yangzhou, China [8]Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Anhui Provincial Innovation Institute for Pharmaceutical Basic Research, Innovative Institute of Tumor Immunity and Medicine (ITIM), Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy, Hefei, China [*1]Medical College, Yangzhou University, Yangzhou, China [*2]Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Anhui Provincial Innovation Institute for Pharmaceutical Basic Research, Innovative Institute of Tumor Immunity and Medicine (ITIM), Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy, Hefei, China [*3]The Yangzhou School of Clinical Medicine of Nanjing Medical University, Yangzhou, China.
推荐引用方式(GB/T 7714)：
Wu Jun,Chen Yong,Zou Hui,et al.6-Phosphogluconate dehydrogenase promotes glycolysis and fatty acid synthesis by inhibiting the AMPK pathway in lung adenocarcinoma cells[J].Cancer Letters.2024,601:217177.doi:10.1016/j.canlet.2024.217177.
APA：
Wu Jun,Chen Yong,Zou Hui,Xu Kaiyue,Hou Jiaqi...&Wang Xiaolin.(2024).6-Phosphogluconate dehydrogenase promotes glycolysis and fatty acid synthesis by inhibiting the AMPK pathway in lung adenocarcinoma cells.Cancer Letters,601,
MLA：
Wu Jun,et al."6-Phosphogluconate dehydrogenase promotes glycolysis and fatty acid synthesis by inhibiting the AMPK pathway in lung adenocarcinoma cells".Cancer Letters 601.(2024):217177

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