Revisited Metabolic Control and Reprogramming Cancers by Means of the Warburg Effect in Tumor Cells

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(17), P. 10037 - 10037

Published: Sept. 2, 2022

Aerobic glycolysis is an emerging hallmark of many human cancers, as cancer cells are defined a “metabolically abnormal system”. Carbohydrates metabolically reprogrammed by its metabolizing and catabolizing enzymes in such cells. Normal acquire their energy from oxidative phosphorylation, while glycolysis, known the “Warburg effect”. Energy–metabolic differences easily found growth, invasion, immune escape anti-tumor drug resistance The pathway carried out multiple enzymatic steps yields two pyruvate molecules one glucose (Glc) molecule orchestral reaction enzymes. Uncontrolled or abnormally activated observed metabolism with enhanced levels glycolytic proteins activities. In effect”, tumor utilize supplied lactic acid-based fermentative operated glycolysis-specific hexokinase (HK), keto-HK-A, Glc-6-phosphate isomerase, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase, phosphofructokinase (PFK), phosphor-Glc isomerase (PGI), fructose-bisphosphate aldolase, phosphoglycerate (PG) kinase (PGK)1, triose phosphate PG mutase (PGAM), glyceraldehyde-3-phosphate dehydrogenase, enolase, isozyme type M2 (PKM2), dehydrogenase (PDH), PDH lactate dehydrogenase. They related to flux. key involved directly linked oncogenesis resistance. Among metabolic enzymes, PKM2, PGK1, HK, keto-HK-A nucleoside diphosphate also have protein Because glycolysis-generated not enough, cell-favored produce low ATP level seems be non-efficient for growth self-protection. Thus, Warburg effect still attractive phenomenon understand favored cancer. If basic properties effect, including genetic mutations signaling shifts considered, anti-cancer therapeutic targets can raised. Specific therapeutics targeting aerobic hypoxic microenvironments been developed kill present review deals tumor-specific revisited viewpoint recent progress.

Language: Английский

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Cross-talk of inflammation and chondrocyte intracellular metabolism in osteoarthritis

Osteoarthritis and Cartilage, Journal Year: 2023, Volume and Issue: 31(8), P. 1012 - 1021

Published: April 23, 2023

Language: Английский

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Oxidative stress regulation and related metabolic pathways in epithelial–mesenchymal transition of breast cancer stem cells

Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 28, 2023

Abstract Epithelial–mesenchymal transition (EMT) is a cell remodeling process in which epithelial cells undergo reversible phenotype switch via the loss of adhesion capacity and acquisition mesenchymal characteristics. In other words, EMT activation can increase invasiveness metastatic properties, prevent sensitivity tumor to chemotherapeutics, as have higher resistance chemotherapy immunotherapy. orchestrated by complex multifactorial network, often linked episodic, transient, or partial events. A variety factors been implicated development. Based on this concept, multiple metabolic pathways master transcription factors, such Snail, Twist, ZEB, drive EMT. Emerging evidence suggests that oxidative stress plays significant role induction. One emerging theory reducing mitochondrial-derived reactive oxygen species production may contribute This review describes how are induction addresses involvement signaling pathways.

Language: Английский

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Glycolysis in the tumor microenvironment: a driver of cancer progression and a promising therapeutic target

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: June 12, 2024

Even with sufficient oxygen, tumor cells use glycolysis to obtain the energy and macromolecules they require multiply, once thought be a characteristic of known as "Warburg effect". In fact, throughout process carcinogenesis, immune stromal cells, two major cellular constituents microenvironment (TME), also undergo thorough metabolic reprogramming, which is typified by increased glycolysis. this review, we provide full-scale review glycolytic remodeling several types TME show how these behave in acidic milieu created glucose shortage lactate accumulation result Notably, an overview putative targets inhibitors along viability using combination immunotherapy chemotherapy. Understanding situations diverse within immunological will aid creation subsequent treatment plans.

Language: Английский

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Metagenome reveals the possible mechanism that microbial strains promote methanogenesis during anaerobic digestion of food waste

Environmental Research, Journal Year: 2024, Volume and Issue: 251, P. 118723 - 118723

Published: March 14, 2024

Language: Английский

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Design, Synthesis, Antibacterial Activity, and Mechanisms of Novel Benzofuran Derivatives Containing Disulfide Moieties

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(18), P. 10195 - 10205

Published: April 25, 2024

The unsatisfactory effects of conventional bactericides and antimicrobial resistance have increased the challenges in managing plant diseases caused by bacterial pests. Here, we report successful design synthesis benzofuran derivatives using as core skeleton splicing disulfide moieties commonly seen natural substances with antibacterial properties. Most our developed benzofurans displayed remarkable activities to frequently encountered pathogens, including Xanthomonas oryzae pv (Xoo), oryzicola (Xoc), axonopodis citri (Xac). With assistance three-dimensional quantitative constitutive relationship (3D-QSAR) model, optimal compound V40 was obtained, which has better vitro activity EC50 values 0.28, 0.56, 10.43 μg/mL against Xoo, Xoc, Xac, respectively, than those positive control, TC (66.41, 78.49, 120.36 μg/mL) allicin (8.40, 28.22, 88.04 μg/mL). Combining results proteomic analysis enzyme assay allows mechanism be preliminarily revealed, suggesting its potential a versatile bactericide combating pests future.

Language: Английский

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Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2

Molecular Oncology, Journal Year: 2021, Volume and Issue: 15(12), P. 3639 - 3658

Published: Aug. 12, 2021

Dysregulation of deubiquitination has been reported to contribute carcinogenesis. However, the function and mechanism deubiquitinating enzyme 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) in progression ovarian cancer (OV), deadliest gynecological cancer, still remains be characterized. The present study demonstrated that PSMD14 was overexpressed OV tissues its higher levels correlated with a International Federation Gynecology Obstetrics (FIGO) stage patients. A high level expression related poor survival Knockdown overexpression experiments elucidated stimulated cell proliferation, invasion, migration vitro. Repression suppressed tumor growth vivo. inhibitor O-phenanthroline (OPA) effectively attenuated malignant behaviors cells vitro Mechanistically, we uncovered involved post-translational regulation pyruvate kinase M2 isoform (PKM2). decreased K63-linked ubiquitination on PKM2, downregulated ratio PKM2 tetramers dimers monomers, subsequently diminished activity induced nuclear translocation contributing aerobic glycolysis cells. Collectively, our findings highlight potential roles as biomarker therapeutic candidate for OV.

Language: Английский

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OGA activated glycopeptide-based nano-activator to activate PKM2 tetramerization for switching catabolic pathways and sensitizing chemotherapy resistance

Biomaterials, Journal Year: 2022, Volume and Issue: 284, P. 121523 - 121523

Published: April 12, 2022

Language: Английский

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Pyruvate Kinase M2 Protects Heart from Pressure Overload‐Induced Heart Failure by Phosphorylating RAC1

Journal of the American Heart Association, Journal Year: 2022, Volume and Issue: 11(11)

Published: June 3, 2022

Background Heart failure, caused by sustained pressure overload, remains a major public health problem. PKM (pyruvate kinase M) acts as rate‐limiting enzyme of glycolysis. PKM2 M2), an alternative splicing product PKM, plays complex roles in various biological processes and diseases. However, the role development heart failure unknown. Methods Results Cardiomyocyte‐specific Pkm2 knockout mice were generated crossing floxed with α‐MHC (myosin heavy chain)‐Cre transgenic mice, cardiac specific overexpression established injecting adeno‐associated virus serotype 9 system. The results showed that cardiomyocyte‐specific deletion resulted significant deterioration functions under whereas mitigated transverse aortic constriction‐induced hypertrophy improved functions. Mechanistically, we demonstrated acted protein rather than pyruvate kinase, which inhibited activation RAC1 (rho family, small GTP binding protein)‐MAPK (mitogen‐activated kinase) signaling pathway phosphorylating progress failure. In addition, blockade through NSC23766, inhibitor, attenuated pathological remodeling deficiency subjected to constriction. Conclusions This study revealed overload‐induced provides attractive target for prevention treatment cardiomyopathies.

Language: Английский

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Small Extracellular Vesicles and Their Involvement in Cancer Resistance: An Up-to-Date Review

Cells, Journal Year: 2022, Volume and Issue: 11(18), P. 2913 - 2913

Published: Sept. 17, 2022

In recent years, tremendous progress has been made in understanding the roles of extracellular vesicles (EVs) cancer. Thanks to advancements molecular biology, it found that fraction EVs called exosomes or small (sEVs) modulates sensitivity cancer cells chemotherapeutic agents by delivering molecularly active non-coding RNAs (ncRNAs). An in-depth analysis shows two main mechanisms are involved exosomal modified chemoresistance: (1) translational repression anti-oncogenes microRNAs (miRs) and (2) lack oncogenes sponging miRs through long (lncRNAs) circular (circRNAs). At cellular level, these processes increase proliferation survival improve their ability metastasize resist apoptosis. addition, studies animal models have shown enhancing tumor size under influence ncRNAs. Ultimately, ncRNAs responsible for clinically significant chemotherapy failures patients with different types Preliminary data also revealed can overcome agent resistance, but results thoroughly fragmented. This review presents how modulate response agents. Understanding interfere chemoresistance may become a milestone developing new therapeutic options, more still required.

Language: Английский

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