4-Hydroxyphenylpyruvate Dioxygenase-Like Protein Promotes Pancreatic Cancer Cell Progression and Is Associated With Glutamine-Mediated Redox Balance Article Swipe

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Xianglai Ye , Xiujuan Wei , Jing Liao , Peipei Chen , Xueyun Li , Yulong Chen , Yue Yang , Qiongya Zhao , Hongwei Sun , Liming Pan , Guorong Chen , Xujun He , Jianxin Lyu , Hezhi Fang ·

YOU? · · 2021 · Open Access · · DOI: https://doi.org/10.3389/fonc.2020.617190

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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Glutamine Cancer cell Cell biology Bioenergetics Carcinogenesis Biology Mitochondrion Mitochondrial intermembrane space Biochemistry Chemistry Cancer Amino acid Gene Genetics Escherichia coli Bacterial outer membrane

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Type: article
Language: en
Landing Page: https://doi.org/10.3389/fonc.2020.617190
OA Status: gold
Cited By: 24
References: 62
Related Works: 10
OpenAlex ID: https://openalex.org/W3121538857

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DOI: https://doi.org/10.3389/fonc.2020.617190

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Title: 4-Hydroxyphenylpyruvate Dioxygenase-Like Protein Promotes Pancreatic Cancer Cell Progression and Is Associated With Glutamine-Mediated Redox Balance

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Language: en

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Publication year: 2021

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Publication date: 2021-01-18

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Authors: Xianglai Ye, Xiujuan Wei, Jing Liao, Peipei Chen, Xueyun Li, Yulong Chen, Yue Yang, Qiongya Zhao, Hongwei Sun, Liming Pan, Guorong Chen, Xujun He, Jianxin Lyu, Hezhi Fang

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Landing page: https://doi.org/10.3389/fonc.2020.617190

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Concepts: Glutamine, Cancer cell, Cell biology, Bioenergetics, Carcinogenesis, Biology, Mitochondrion, Mitochondrial intermembrane space, Biochemistry, Chemistry, Cancer, Amino acid, Gene, Genetics, Escherichia coli, Bacterial outer membrane

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Cited by: 24

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abstract_inverted_index.protein	45, 100
abstract_inverted_index.results	118
abstract_inverted_index.through	148
abstract_inverted_index.whereas	79
abstract_inverted_index.balance.	156
abstract_inverted_index.conclude	142
abstract_inverted_index.inhibits	83
abstract_inverted_index.process,	29
abstract_inverted_index.promotes	74, 145
abstract_inverted_index.protects	123
abstract_inverted_index.protein,	50
abstract_inverted_index.adenosine	108
abstract_inverted_index.dependent	115
abstract_inverted_index.glutamine	114, 137, 152
abstract_inverted_index.including	30
abstract_inverted_index.knockdown	80
abstract_inverted_index.localized	99
abstract_inverted_index.metabolic	6, 12, 18, 131
abstract_inverted_index.oxidative	126
abstract_inverted_index.processes	106
abstract_inverted_index.regulates	103
abstract_inverted_index.associated	53
abstract_inverted_index.formation.	88
abstract_inverted_index.generation	111
abstract_inverted_index.mechanisms	8
abstract_inverted_index.metabolism	153
abstract_inverted_index.pancreatic	58
abstract_inverted_index.positively	52, 102
abstract_inverted_index.previously	48
abstract_inverted_index.prognosis.	64
abstract_inverted_index.development	56
abstract_inverted_index.hemostasis.	36
abstract_inverted_index.metabolism.	138
abstract_inverted_index.production,	32
abstract_inverted_index.significant	25
abstract_inverted_index.bioenergetic	105
abstract_inverted_index.mitochondria	22
abstract_inverted_index.progression.	16
abstract_inverted_index.triphosphate	109
abstract_inverted_index.biosynthesis,	33
abstract_inverted_index.intermembrane	97
abstract_inverted_index.mitochondrial	96, 104
abstract_inverted_index.proliferation	85
abstract_inverted_index.reprogramming	7, 129
abstract_inverted_index.tumorigenesis	75
abstract_inverted_index.adenocarcinoma	60
abstract_inverted_index.overexpression	68
abstract_inverted_index.uncharacterized	49
abstract_inverted_index.Mechanistically,	89
abstract_inverted_index.dioxygenase-like	44
abstract_inverted_index.4-hydroxyphenylpyruvate	43
cited_by_percentile_year.max	99
cited_by_percentile_year.min	96
corresponding_author_ids	https://openalex.org/A5091548233, https://openalex.org/A5033069020
countries_distinct_count	1
institutions_distinct_count	14
corresponding_institution_ids	https://openalex.org/I27781120, https://openalex.org/I4210131061, https://openalex.org/I4210165441
sustainable_development_goals[0].id	https://metadata.un.org/sdg/7
sustainable_development_goals[0].score	0.6700000166893005
sustainable_development_goals[0].display_name	Affordable and clean energy
citation_normalized_percentile.value	0.84679496
citation_normalized_percentile.is_in_top_1_percent	False
citation_normalized_percentile.is_in_top_10_percent	False