How Warburg-Associated Lactic Acidosis Rewires Cancer Cell Energy Metabolism to Resist Glucose Deprivation DOI Open Access

Zoé Daverio,

Aneta Balcerczyk, Gilles J. P. Rautureau

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(5), P. 1417 - 1417

Published: Feb. 23, 2023

Lactic acidosis, a hallmark of solid tumour microenvironment, originates from lactate hyperproduction and its co-secretion with protons by cancer cells displaying the Warburg effect. Long considered side effect metabolism, lactic acidosis is now known to play major role in physiology, aggressiveness treatment efficiency. Growing evidence shows that it promotes cell resistance glucose deprivation, common feature tumours. Here we review current understanding how extracellular acting as combination enzymatic inhibitors, signal, nutrient, switch metabolism an oxidative metabolic phenotype, which allows withstand makes promising anticancer target. We also discuss about acidosis’ could be integrated whole-tumour what perspectives opens up for future research.

Language: Английский

LncRNA CCAT1 facilitates the progression of gastric cancer via PTBP1-mediated glycolysis enhancement DOI Creative Commons
Cong Zhang, Huixia Wang, Qingwei Liu

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: Sept. 23, 2023

Gastric cancer (GC) is one of the most prevalent malignant tumors digestive system. As a hallmark cancer, energy-related metabolic reprogramming manipulated by multiple factors, including long non-coding RNAs (lncRNAs). Notably, lncRNA CCAT1 has been identified as crucial regulator in tumor progression. Nevertheless, precise molecular mechanisms underlying involvement GC remain unclear. Gain- and loss-of-function experiments were performed to evaluate roles tumorigenesis glycolysis GC. Bioinformatics analyses mechanistic experiments, such mass spectrometry (MS), RNA-pulldown, RNA immunoprecipitation (RIP), employed reveal potential interacting protein elucidate regulatory mechanism glycolysis. Moreover, nude mice xenograft assay was used effect on cells vivo. In this study, we that expression significantly elevated tissues plasma exosomes patients, well cell lines. Functional showed knockdown resulted substantial decrease proliferation, migration invasion both vitro vivo through decreasing glycolytic enzymes rate. Conversely, overexpression exhibited contrasting effects. Mechanistically, interacted with PTBP1 effectively maintained its stability inhibiting ubiquitin-mediated degradation process. critical splicing factor, facilitated transition from PKM1 PKM2, thereby augmenting activity ultimately fostering progression Our findings demonstrate plays significant role promoting migration, PTBP1/PKM2/glycolysis pathway, thus suggesting CCAT1's biomarker therapeutic target for

Language: Английский

Citations

24
The role of glycolytic metabolic pathways in cardiovascular disease and potential therapeutic approaches DOI Creative Commons
Shuxian Chen, Yuanming Zou, Chunyu Song

et al.

Basic Research in Cardiology, Journal Year: 2023, Volume and Issue: 118(1)

Published: Nov. 8, 2023

Abstract Cardiovascular disease (CVD) is a major threat to human health, accounting for 46% of non-communicable deaths. Glycolysis conserved and rigorous biological process that breaks down glucose into pyruvate, its primary function provide the body with energy intermediate products needed life activities. The non-glycolytic actions enzymes associated glycolytic pathway have long been found be development CVD, typically exemplified by metabolic remodeling in heart failure, which condition exhibits rapid adaptive response hypoxic conditions, occurring early course failure. It mainly characterized decrease oxidative phosphorylation rise pathway, glycolysis considered hallmark remodeling. In addition this, main source cardiomyocytes during ischemia–reperfusion. Not only that, auxiliary pathways glycolysis, such as polyol hexosamine pentose phosphate are also closely related CVD. Therefore, targeting very attractive therapeutic intervention However, relationship between CVD complex, some preclinical studies confirmed does certain degree efficacy, but specific role has yet explored. This article aims summarize current knowledge regarding key (including hexokinase (HK), phosphoglucose isomerase (PGI), phosphofructokinase-1 (PFK1), aldolase (Aldolase), phosphoglycerate metatase (PGAM), enolase (ENO) pyruvate kinase (PKM) lactate dehydrogenase (LDH)) their cardiovascular diseases (e.g., myocardial infarction, atherosclerosis) possible emerging targets.

Language: Английский

Citations

24
NIR-II imaging-guided precise photodynamic therapy for augmenting tumor-starvation therapy by glucose metabolism reprogramming interference DOI
Xiawei Wu, Yong Fan, Kairuo Wang

et al.

Science Bulletin, Journal Year: 2024, Volume and Issue: 69(9), P. 1263 - 1274

Published: Feb. 9, 2024

Language: Английский

Citations

15
Targeting tumor-intrinsic SLC16A3 to enhance anti-PD-1 efficacy via tumor immune microenvironment reprogramming DOI Creative Commons
Ting Yu, Zhaoyun Liu,

Qingxu Tao

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 589, P. 216824 - 216824

Published: March 23, 2024

Immunotherapy, especially immune checkpoint inhibitors, has revolutionized clinical practice within the last decade. However, primary and secondary resistance to immunotherapy is common in patients with diverse types of cancer. It well-acknowledged that tumor cells can facilitate formation immunosuppressive microenvironments via metabolism reprogramming, lactic acid, metabolite glycolysis, a significant contributor. SLC16A3 (also named as MCT4) transporter mediating acid efflux. In this study, we investigated role glycolysis aimed improve effects Slc16a3 inhibition. Bioinformatical analysis revealed expression glycolysis-related genes correlated less CD8

Language: Английский

Citations

14
Exploring the mystery of tumor metabolism: Warburg effect and mitochondrial metabolism fighting side by side DOI
Yongxin Yu,

Yulang Jiang,

Christian Glandorff

et al.

Cellular Signalling, Journal Year: 2024, Volume and Issue: 120, P. 111239 - 111239

Published: May 28, 2024

Language: Английский

Citations

14
Comprehensive review of histone lactylation: Structure, function, and therapeutic targets DOI

Kaiwen Xu,

Zhang Keyi,

Yanshuang Wang

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 225, P. 116331 - 116331

Published: May 29, 2024

Language: Английский

Citations

13
The role of targeting glucose metabolism in chondrocytes in the pathogenesis and therapeutic mechanisms of osteoarthritis: a narrative review DOI Creative Commons

Peng Pi,

Liqing Zeng,

Zhipeng Zeng

et al.

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: March 6, 2024

Osteoarthritis (OA) is a common degenerative joint disease that can affect almost any joint, mainly resulting in dysfunction and pain. Worldwide, OA affects more than 240 million people one of the leading causes activity limitation adults. However, pathogenesis remains elusive, lack well-established clinical treatment strategies. Recently, energy metabolism alterations have provided new insights into OA. Accumulating evidence indicates glucose plays key role maintaining cartilage homeostasis. Disorders lead to chondrocyte hypertrophy extracellular matrix degradation, promote occurrence development This article systematically summarizes regulatory effects different enzymes factors related OA, as well mechanism potential various substances by affecting metabolism. provides theoretical basis for better understanding progression optimal prevention

Language: Английский

Citations

12
Metabolism-regulating non-coding RNAs in breast cancer: roles, mechanisms and clinical applications DOI Creative Commons

Shiliang Xu,

Lingxia Wang,

Yuexin Zhao

et al.

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: Feb. 26, 2024

Abstract Breast cancer is one of the most common malignancies that pose a serious threat to women's health. Reprogramming energy metabolism major feature malignant transformation breast cancer. Compared normal cells, tumor cells reprogram metabolic processes more efficiently, converting nutrient supplies into glucose, amino acid and lipid required for proliferation progression. Non-coding RNAs(ncRNAs) are class functional RNA molecules not translated proteins but regulate expression target genes. NcRNAs have been demonstrated be involved in various aspects metabolism, including glycolysis, glutaminolysis, fatty synthesis. This review focuses on regulatory mechanisms clinical applications metabolism-regulating ncRNAs We summarize vital roles played by endocrine therapy, targeted chemotherapy, immunotherapy, radiotherapy resistance cancer, as well their potential therapeutic targets biomarkers. Difficulties perspectives current non-coding strategies discussed.

Language: Английский

Citations

10
The role of lncRNA NEAT1 in human cancer chemoresistance DOI Creative Commons
Feng Long,

Xue Li,

Jingyu Pan

et al.

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: July 5, 2024

Abstract Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance an important reason for poor efficacy and prognosis, which has become urgent problem to be solved field chemotherapy. Therefore, it very deeply study analyze mechanism its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) been shown closely associated with cancer. NEAT1 induces cell chemotherapeutic drugs by regulating apoptosis, cycle, drug transport metabolism, DNA damage repair, EMT, autophagy, stem characteristics, metabolic reprogramming. This indicates that may target overcome expected a potential biomarker predict effect article summarizes expression characteristics different cancers, discusses role related molecular mechanisms, aiming clarify as new feasibility sensitizers, view providing therapeutic direction overcoming dilemma future.

Language: Английский

Citations

10
METTL1 coordinates cutaneous squamous cell carcinoma progression via the m7G modification of the ATF4 mRNA DOI Creative Commons
Xinru Zhang, Tong Chen,

Fanrong Zhang

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 27, 2025

Abstract Methyltransferase-like 1 (METTL1)-mediated m7G modification is a common occurrence in various RNA species, including mRNAs, tRNAs, rRNAs, and miRNAs. Recent evidence suggests that this linked to the development of several cancers, making it promising target for cancer therapy. However, specific role cutaneous squamous cell carcinoma (cSCC) not well understood. In study, we observed conspicuously elevated levels METTL1 cSCC tumors lines. Inhibiting led reduced survival, migration, invasion, xenograft tumor growth cells. Mechanistically, through combination sequencing, methylated immunoprecipitation (MeRIP)-qPCR, mRNA stability assays, discovered responsible ATF4 mRNA, leading increased expression ATF4. Importantly, demonstrated dependent on methyltransferase activity METTL1. Additionally, positive association between tumors. Intriguingly, restoring cells only promoted glycolysis but also reversed anti-tumor effects knockdown. conclusion, our results underscore critical tumorigenesis, suggesting future therapies.

Language: Английский

Citations

1