机构：[1]State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy andTianjin Key Laboratory of Molecular Drug Research, Nankai University, 300350Tianjin, China[2]The First Affiliated Hospital, Biomedical Translational ResearchInstitute, Jinan University, 510632 Guangzhou, Guangdong, China[3]Department of Clinical Biological Resource Bank, Guangzhou Institute ofPediatrics, Guangzhou Women and Children’s Medical Center, GuangzhouMedical University, 510623 Guangzhou, Guangdong, China[4]Department ofMedical Biochemistry and Molecular Biology, School of Medicine, JinanUniversity, 510632 Guangzhou, Guangdong, China[5]Department ofPharmacology, School of Medicine, Jinan University, 510632 Guangzhou,Guangdong, China[6]Department of Pathology, Medical School, DalianUniversity, 116622 Dalian, Liaoning, China[7]School of Integrative Medicine,Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China
4-hydroxyphenylpyruvate dioxygenase (HPD) is an important modifier of tyrosine metabolism. However, the precise contribution of HPD to cancer metabolism and tumorigenesis remains unclear. In this study, we found that HPD was highly expressed in lung cancer and its higher expression correlated with poor prognosis in lung cancer patients. Suppressed HPD expression was sufficient to decrease oxidative pentose phosphate pathway (PPP) flux, leading to reduced RNA biosynthesis and enhanced reactive oxygen species (ROS) level, attenuated cancer cell proliferation, and tumor growth. Mechanistically, HPD not only promotes tyrosine catabolism leading to increased acetyl-CoA levels, the source of histone acetylation, but also stimulates histone deacetylase 10 (HDAC10) translocation from the nucleus into the cytoplasm mediated by tumor suppressor liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) signaling. Both controlled histone acetylation modification, which enhanced transcription of the important PPP enzyme Glucose-6-Phosphate Dehydrogenase (G6PD). Thus, this study reveals HPD as a novel regulator of LKB1-AMPK signaling-mediated HDAC10 nuclear location, which contributes to G6PD expression in promoting tumor growth, which is a promising target for lung cancer treatment.
基金：
We thank Dr. Shannon Elf (The University of Chicago) for critical review and
edit of the paper. We are grateful to Dr. Chenglai Xia for providing normal
proliferating human bronchial epithelial cell line (BEAS-2B), and Dr. Tongzheng
Liu for providing AMPK WT and KO MEF cells. This work was supported by the
National Nature Science Foundation of China (81672781, 81702746, and
31560312), the Startup Fund for Distinguished Scholars from Nankai University,
the Program from the Science and Technology Department of Guangdong Province of China (Grant 2017A030313890, 2016A030310088), the Science and
Technology Program of Guangzhou (Grant 201807010003), and the
Fundamental Research Funds for the Central Universities (21616323,
21617433). This work was also supported by the China Postdoctoral Science
Foundation (2017M612839), and the Program of Introducing Talents of
Discipline to Universities (111 Project, No. B16021).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类|2 区生物
小类|2 区细胞生物学
最新[2025]版：
大类|1 区生物学
小类|2 区细胞生物学
第一作者：
第一作者机构：[1]State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy andTianjin Key Laboratory of Molecular Drug Research, Nankai University, 300350Tianjin, China[2]The First Affiliated Hospital, Biomedical Translational ResearchInstitute, Jinan University, 510632 Guangzhou, Guangdong, China
共同第一作者：
通讯作者：
通讯机构：[1]State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy andTianjin Key Laboratory of Molecular Drug Research, Nankai University, 300350Tianjin, China[2]The First Affiliated Hospital, Biomedical Translational ResearchInstitute, Jinan University, 510632 Guangzhou, Guangdong, China
推荐引用方式(GB/T 7714)：
Changliang Shan,Zhaoliang Lu,Zhen Li,et al.4-hydroxyphenylpyruvate dioxygenase promotes lung cancer growth via pentose phosphate pathway (PPP) flux mediated by LKB1-AMPK/HDAC10/G6PD axis.[J].Cell death & disease.2019,10(7):525.doi:10.1038/s41419-019-1756-1.
APA：
Changliang Shan,Zhaoliang Lu,Zhen Li,Hao Sheng,Jun Fan...&Shuai Zhang.(2019).4-hydroxyphenylpyruvate dioxygenase promotes lung cancer growth via pentose phosphate pathway (PPP) flux mediated by LKB1-AMPK/HDAC10/G6PD axis..Cell death & disease,10,(7)
MLA：
Changliang Shan,et al."4-hydroxyphenylpyruvate dioxygenase promotes lung cancer growth via pentose phosphate pathway (PPP) flux mediated by LKB1-AMPK/HDAC10/G6PD axis.".Cell death & disease 10..7(2019):525
生物学