Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Feb. 17, 2023

Abstract Having a hypoxic microenvironment is common and salient feature of most solid tumors. Hypoxia has profound effect on the biological behavior malignant phenotype cancer cells, mediates effects chemotherapy, radiotherapy, immunotherapy through complex mechanisms, closely associated with poor prognosis in various patients. Accumulating studies have demonstrated that normalization tumor vasculature, nanoparticle carriers biocarriers can effectively increase oxygen concentration microenvironment, improve drug delivery efficacy radiotherapy. They also infiltration innate adaptive anti-tumor immune cells to enhance immunotherapy. Furthermore, drugs targeting key genes hypoxia, including hypoxia tracers, hypoxia-activated prodrugs, hypoxia-inducible factors downstream targets, be used for visualization quantitative analysis antitumor activity. However, relationship between an area research requires further exploration. Here, we investigated potential development cancer, changes signaling pathways occur adapt environments, mechanisms hypoxia-induced tolerance, chemotherapeutic enhanced radiation as well insights applications therapy.

Language: Английский

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Modulation of cellular processes by histone and non-histone protein acetylation

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(5), P. 329 - 349

Published: Jan. 18, 2022

Language: Английский

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Histone lactylation drives oncogenesis by facilitating m6A reader protein YTHDF2 expression in ocular melanoma

Genome biology, Journal Year: 2021, Volume and Issue: 22(1)

Published: March 16, 2021

Histone lactylation, a metabolic stress-related histone modification, plays an important role in the regulation of gene expression during M1 macrophage polarization. However, lactylation tumorigenesis remains unclear.Here, we show is elevated tumors and associated with poor prognosis ocular melanoma. Target correction aberrant triggers therapeutic efficacy both vitro vivo. Mechanistically, contributes to by facilitating YTHDF2 expression. Moreover, recognizes m6A modified PER1 TP53 mRNAs promotes their degradation, which accelerates melanoma.We reveal oncogenic thereby providing novel targets for melanoma therapy. We also bridge modifications RNA modifications, provides understanding epigenetic tumorigenesis.

Language: Английский

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Lactate as a fulcrum of metabolism

Redox Biology, Journal Year: 2020, Volume and Issue: 35, P. 101454 - 101454

Published: Feb. 9, 2020

Mistakenly thought to be the consequence of oxygen lack in contracting skeletal muscle we now know that L-enantiomer lactate anion is formed under fully aerobic conditions and utilized continuously diverse cells, tissues, organs at whole-body level. By shuttling between producer (driver) consumer (recipient) cells fulfills least three purposes: 1] a major energy source for mitochondrial respiration; 2] gluconeogenic precursor; 3] signaling molecule. Working by mass action, cell redox regulation, allosteric binding, reprogramming chromatin lactylation lysine residues on histones, has influences substrate partitioning. The physiological range tissue [lactate] 0.5-20 mM cellular Lactate/Pyruvate ratio (L/P) can from 10 >500; these changes during exercise other stress-strain responses dwarf metabolic signals magnitude span. Hence, dynamics have rapid short- long-term effects control systems. inhibiting lipolysis adipose via HCAR-1, fatty acid uptake malonyl-CoA CPT1, controls Repeated exposure regular results expression regulatory enzymes glycolysis respiration. Lactate fulcrum regulation vivo.

Language: Английский

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Metabolic reprogramming and epigenetic modifications on the path to cancer

Protein & Cell, Journal Year: 2021, Volume and Issue: 13(12), P. 877 - 919

Published: May 29, 2021

Abstract Metabolic rewiring and epigenetic remodeling, which are closely linked reciprocally regulate each other, among the well-known cancer hallmarks. Recent evidence suggests that many metabolites serve as substrates or cofactors of chromatin-modifying enzymes a consequence translocation spatial regionalization metabolites. Various metabolic alterations modifications also reportedly drive immune escape impede immunosurveillance within certain contexts, playing important roles in tumor progression. In this review, we focus on how reprogramming cells reshapes alterations, particular acetylation methylation histone proteins DNA. We discuss other eminent such as, succinylation, hydroxybutyrylation, lactylation, update current advances metabolism- modification-based therapeutic prospects cancer.

Language: Английский

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Metabolites and the tumour microenvironment: from cellular mechanisms to systemic metabolism

Nature Metabolism, Journal Year: 2021, Volume and Issue: 3(1), P. 21 - 32

Published: Jan. 4, 2021

Language: Английский

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Lactylation-driven METTL3-mediated RNA m6A modification promotes immunosuppression of tumor-infiltrating myeloid cells

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(9), P. 1660 - 1677.e10

Published: March 22, 2022

Language: Английский

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Determinants of Resident Tissue Macrophage Identity and Function

Immunity, Journal Year: 2020, Volume and Issue: 52(6), P. 957 - 970

Published: June 1, 2020

Language: Английский

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Glycolysis – a key player in the inflammatory response

FEBS Journal, Journal Year: 2020, Volume and Issue: 287(16), P. 3350 - 3369

Published: April 7, 2020

The inflammatory response involves the activation of several cell types to fight insults caused by a plethora agents, and maintain tissue homoeostasis. On one hand, cells involved in pro‐inflammatory response, such as M1 macrophages, Th1 Th17 lymphocytes or activated microglia, must rapidly provide energy fuel inflammation, which is essentially accomplished glycolysis high lactate production. other regulatory T M2 are immune regulation resolution preferentially use fatty acid oxidation through TCA cycle main source for Here, we discuss impact glycolytic metabolism at different steps response. Finally, review wide variety molecular mechanisms could explain relationship between metabolites phenotype, including signalling events, epigenetic remodelling, post‐transcriptional post‐translational modifications. Inflammatory processes common feature many age‐associated diseases, cardiovascular neurodegenerative disorders. finding that immunometabolism be master regulator inflammation broadens avenue treating inflammation‐related pathologies manipulation vascular metabolism.

Language: Английский

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Lactate promotes macrophage HMGB1 lactylation, acetylation, and exosomal release in polymicrobial sepsis

Cell Death and Differentiation, Journal Year: 2021, Volume and Issue: 29(1), P. 133 - 146

Published: Aug. 6, 2021

High circulating levels of lactate and high mobility group box-1 (HMGB1) are associated with the severity mortality sepsis. However, it is unclear whether could promote HMGB1 release during The present study demonstrated a novel role in lactylation acetylation macrophages polymicrobial We found that can uptake extracellular via monocarboxylate transporters (MCTs) to p300/CBP-dependent mechanism. also observed stimulates by Hippo/YAP-mediated suppression deacetylase SIRT1 β-arrestin2-mediated recruitment acetylases p300/CBP nucleus G protein-coupled receptor 81 (GPR81). lactylated/acetylated released from exosome secretion which increases endothelium permeability. In vivo reduction production and/or inhibition GPR81-mediated signaling decreases exosomal improves survival outcome Our results provide basis for targeting lactate/lactate-associated combat

Language: Английский

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