Frontiers in Oncology (Jan 2021)
4-Hydroxyphenylpyruvate Dioxygenase-Like Protein Promotes Pancreatic Cancer Cell Progression and Is Associated With Glutamine-Mediated Redox Balance
- Xianglai Ye,
- Xianglai Ye,
- Xianglai Ye,
- Xiujuan Wei,
- Xiujuan Wei,
- Xiujuan Wei,
- Jing Liao,
- Jing Liao,
- Jing Liao,
- Peipei Chen,
- Peipei Chen,
- Peipei Chen,
- Xueyun Li,
- Xueyun Li,
- Xueyun Li,
- Yulong Chen,
- Yulong Chen,
- Yulong Chen,
- Yue Yang,
- Yue Yang,
- Yue Yang,
- Qiongya Zhao,
- Hongwei Sun,
- Liming Pan,
- Guorong Chen,
- Xujun He,
- Jianxin Lyu,
- Jianxin Lyu,
- Jianxin Lyu,
- Jianxin Lyu,
- Jianxin Lyu,
- Hezhi Fang,
- Hezhi Fang,
- Hezhi Fang
Affiliations
- Xianglai Ye
- Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical University, Wenzhou, China
- Xianglai Ye
- Zhejiang Provincial Key Laboratory of Medical Genetics, Department of Cell Biology and Medical Genetics, Wenzhou Medical University, Wenzhou, China
- Xianglai Ye
- College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Xiujuan Wei
- Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical University, Wenzhou, China
- Xiujuan Wei
- Zhejiang Provincial Key Laboratory of Medical Genetics, Department of Cell Biology and Medical Genetics, Wenzhou Medical University, Wenzhou, China
- Xiujuan Wei
- College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Jing Liao
- Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical University, Wenzhou, China
- Jing Liao
- Zhejiang Provincial Key Laboratory of Medical Genetics, Department of Cell Biology and Medical Genetics, Wenzhou Medical University, Wenzhou, China
- Jing Liao
- College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Peipei Chen
- Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical University, Wenzhou, China
- Peipei Chen
- Zhejiang Provincial Key Laboratory of Medical Genetics, Department of Cell Biology and Medical Genetics, Wenzhou Medical University, Wenzhou, China
- Peipei Chen
- College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Xueyun Li
- Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical University, Wenzhou, China
- Xueyun Li
- Zhejiang Provincial Key Laboratory of Medical Genetics, Department of Cell Biology and Medical Genetics, Wenzhou Medical University, Wenzhou, China
- Xueyun Li
- College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Yulong Chen
- Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical University, Wenzhou, China
- Yulong Chen
- Zhejiang Provincial Key Laboratory of Medical Genetics, Department of Cell Biology and Medical Genetics, Wenzhou Medical University, Wenzhou, China
- Yulong Chen
- College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Yue Yang
- Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical University, Wenzhou, China
- Yue Yang
- Zhejiang Provincial Key Laboratory of Medical Genetics, Department of Cell Biology and Medical Genetics, Wenzhou Medical University, Wenzhou, China
- Yue Yang
- College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Qiongya Zhao
- College of Laboratory Medicine, Hangzhou Medical College, Hangzhou, China
- Hongwei Sun
- Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Liming Pan
- Department of Pathology, The People’s Hospital of Yuhuan, The Yuhuan Branch of the First Affiliated Hospital of Wenzhou Medical University, Taizhou, China
- Guorong Chen
- Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Xujun He
- Department of Laboratory Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, China
- Jianxin Lyu
- Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical University, Wenzhou, China
- Jianxin Lyu
- Zhejiang Provincial Key Laboratory of Medical Genetics, Department of Cell Biology and Medical Genetics, Wenzhou Medical University, Wenzhou, China
- Jianxin Lyu
- College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Jianxin Lyu
- College of Laboratory Medicine, Hangzhou Medical College, Hangzhou, China
- Jianxin Lyu
- Department of Laboratory Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, China
- Hezhi Fang
- Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical University, Wenzhou, China
- Hezhi Fang
- Zhejiang Provincial Key Laboratory of Medical Genetics, Department of Cell Biology and Medical Genetics, Wenzhou Medical University, Wenzhou, China
- Hezhi Fang
- College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- DOI
- https://doi.org/10.3389/fonc.2020.617190
- Journal volume & issue
-
Vol. 10
Abstract
Tumor cells develop a series of metabolic reprogramming mechanisms to meet the metabolic needs for tumor progression. As metabolic hubs in cells, mitochondria play a significant role in this process, including energy production, biosynthesis, and redox hemostasis. In this study, we show that 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL), a previously uncharacterized protein, is positively associated with the development of pancreatic ductal adenocarcinoma (PDAC) and disease prognosis. We found that overexpression of HPDL in PDAC cells promotes tumorigenesis in vitro, whereas knockdown of HPDL inhibits cell proliferation and colony formation. Mechanistically, we found that HPDL is a mitochondrial intermembrane space localized protein that positively regulates mitochondrial bioenergetic processes and adenosine triphosphate (ATP) generation in a glutamine dependent manner. Our results further reveal that HPDL protects cells from oxidative stress by reprogramming the metabolic profile of PDAC cells toward glutamine metabolism. In short, we conclude that HPDL promotes PDAC likely through its effects on glutamine metabolism and redox balance.
Keywords
