Journal
FRONTIERS IN ONCOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2020.617190
Keywords
mitochondria; pancreatic ductal adenocarcinoma; metabolic reprogramming; glutamine; redox balance
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Funding
- National Natural Science Foundation of China [31670784, 82072366]
- Natural Science Foundation of Zhejiang Province [Y20H160175]
- Research Fund of National Health Commission
- Major Medical Research Program of Zhejiang Province [WKJ-ZJ-1929]
- Technology and Science Project of Yuhuan City [201741]
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The study identified an uncharacterized protein, HPDL, positively associated with the development and prognosis of pancreatic ductal adenocarcinoma (PDAC). HPDL regulates mitochondrial bioenergetics and glutamine metabolism to promote tumor cell proliferation.
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.
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