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Energy metabolism: a new target for gastric cancer treatment

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Abstract

Gastric cancer is the fifth most common malignancy worldwide having the fourth highest mortality rate. Energy metabolism is key and closely linked to tumour development. Most important in the reprogramming of cancer metabolism is the Warburg effect, which suggests that tumour cells will utilise glycolysis even with normal oxygen levels. Various molecules exert their effects by acting on enzymes in the glycolytic pathway, integral to glycolysis. Second, mitochondrial abnormalities in the reprogramming of energy metabolism, with consequences for glutamine metabolism, the tricarboxylic acid cycle and oxidative phosphorylation, abnormal fatty acid oxidation and plasma lipoprotein metabolism are important components of tumour metabolism. Third, inflammation-induced oxidative stress is a danger signal for cancer. Fourth, patterns of signalling pathways involve all aspects of metabolic transduction, and many clinical drugs exert their anticancer effects through energy metabolic signalling. This review summarises research on energy metabolism genes, enzymes and proteins and transduction pathways associated with gastric cancer, and discusses the mechanisms affecting their effects on postoperative treatment resistance and prognoses of gastric cancer. We believe that an in-depth understanding of energy metabolism reprogramming will aid the diagnosis and subsequent treatment of gastric cancer.

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Data availability

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Abbreviations

GPI:

Glucose-6-phosphate isomerase

TIGAR:

TP53-induced glycolysis and apoptosis regulator

ROS:

Reactive oxygen species

ENO1:

Alpha-enolase

PKM2:

Pyruvate kinase M2

PI3K/AKT:

Phosphatidylinositol 3-kinase/AKT

PolG:

Polymerase gamma

PDHA1:

Pyruvate dehydrogenase A1

PDK:

Pyruvate dehydrogenase kinase

LDHA:

Lactate dehydrogenase A

HIF1-α:

Hypoxia-inducible factor 1-α

CDK2:

Cell cycle-dependent kinase

SETD1A:

SET domain containing 1A

DLC3:

Deleted in liver cancer 3

HMGB2:

High-mobility group box 2

GRINA:

Glutamate receptor ionotropic N-methyl-d-aspartate-associated protein 1

ANXA2:

Membrane-linked protein A2

PCs:

Parietal cells

AMPK:

AMP kinase

SLC2A1:

Solute carrier family 2 member 1

PRKAA1:

Protein kinase AMP-activated α1 catalytic subunit

CircRNAs:

Circular RNAs

Myh9:

Myosin heavy chain 9

REDD1:

Increases DNA damage response 1

TAMs:

Tumour-associated macrophages

TAM:

Tissue-associated macrophage

PINK1:

PTEN-induced kinase 1

IM:

Inner mitochondrial membrane

MRC:

Mitochondrial respiratory chain

CoQ:

Coenzyme Q

MALM:

Mieap-induced accumulation of lysosomes within mitochondria

mtROS:

Mitochondrial reactive oxygen species

mtDNA:

Mitochondrial DNA

JNK:

Jun N-terminal kinase

TRPM2:

Transient receptor potential melastatin-2

PA-2:

Parameritannin A-2

DOX:

Doxorubicin

PAB:

Pseudolaric acid B

ER:

Endoplasmic reticulum

BP:

N-butylidenephthalide

PA:

Poric acid

JAK2:

Janus kinase 2

STAT3:

Signal transducer and activator of transcription 3

NSAID:

Nonsteroidal anti-inflammatory drug

PKC:

Protein kinase C

P38:

P38 MAPK

Drp1:

Dynamin-Related Protein 1

5-FU:

5-Fluorouracil

Mito-FF:

Mitochondria-penetrating tripeptide

PDT:

Photo-dynamic effect

TPT:

Topoisomerase I inhibitor Topotecan

GS:

Glutamine synthetase

ASC:

Alanine-serine-cysteine

ADCC:

Antibody dependent cellular cytotoxicity

GSH:

Glutathione

GA:

Gastric adenocarcinoma

IDH:

Isocitrate dehydrogenase

GC:

Gastric cancer

OXPHOS:

Oxidative phosphorylation

IL-10:

Interleukin 10

SALL4:

Spalt-like transcription factor 4

CAB39L:

Calcium binding protein 39-like

S100A10:

S100 calcium-binding protein A10

CSCs:

Cancer stem-like cells

Prdx3:

Peroxiredoxin 3

ALDH3A1:

Aldehyde dehydrogenase 3A1

FAO:

Fatty acid oxidation

MSCs:

Mesenchymal stem cells

HCP5:

Histocompatibility leukocyte antigen complex P5

Fen:

Fenofibrate

OS:

Oxidative stress

NOXs:

NADPH oxidases

Nrf2:

Nuclear factor erythroid-related factor 2

VLDL:

Very low density lipoprotein

HDLC:

High-density lipoprotein cholesterol

TG:

Triglycerides

TLR2:

Toll-like receptor 2

SGLT1:

Sodium/glucose cotransporter 1

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Acknowledgements

This work was supported by the National key research and development project (NO. 2021YFE0192100), Natural Science Foundation of Hunan Province (NO. 2020JJ4083, NO.2021JJ30694), Science and Technology Innovation Project of Hunan Province (NO. 2020SK51703), Innovation and Entrepreneurship Training Program for College Students in Hunan Province (NO.S202110555296), Key Projects of Hunan Provincial Education Department (NO.21A0285), Natural Science Foundation of Hunan Provincial and Municipal Co-funding (NO.2022JJ50029) , Key projects of Shaoyang Science and Technology Bureau (NO.2021GZ031)

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  1. Cancer Research Institute of Hengyang Medical School, Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, University of South China, 28 Changsheng Road, Hengyang, 421001, Hunan, People’s Republic of China

    Jiangrong Liu, Xue Bai, Meilan Zhang, Xuemei Zeng, Yuwei Li & Zhiwei Zhang

  2. Department of Head and Neck Surgery, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, People’s Republic of China

    Juan Xiao

  3. Department of Pathology, The Second Affiliated Hospital, Shaoyang College, Shaoyang, 422000, Hunan, People’s Republic of China

    Shihua Wu

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  1. Jiangrong Liu
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JL (first auther): Conceptualization; Data curation; Formal analysis; Writing—Original Draft; Writing—review &editing; Had the idea for the article; Performed the literature search and data analysis. XB: Investigation; Supervision; Critically revised the work. MZ: Investigation; Supervision. SW: Investigation; Supervision. JX: Project administration. XZ: Supervision. YL: Investigation. ZZ (Corresponding author): Funding acquisition; Project administration; Supervision. All authors reviewed the manuscript.

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Correspondence to Zhiwei Zhang.

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Liu, J., Bai, X., Zhang, M. et al. Energy metabolism: a new target for gastric cancer treatment. Clin Transl Oncol 26, 338–351 (2024). https://doi.org/10.1007/s12094-023-03278-3

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