Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Ноя. 1, 2022

Colorectal cancer (CRC) is the third most common and second leading cause of cancer-related death worldwide. Countless CRC patients undergo disease progression. As a hallmark cancer, Warburg effect promotes metastasis remodels tumor microenvironment, including promoting angiogenesis, immune suppression, cancer-associated fibroblasts formation drug resistance. Targeting metabolism would be promising method for treatment CRC. In this review, we summarize information about roles in microenvironment to elucidate mechanisms governing identify novel targets therapy.

Язык: Английский

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Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

MedComm, Год журнала: 2023, Номер 4(3)

Опубликована: Май 2, 2023

Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on backbones amino acid side chains proteins and expand diversity proteins, which provides basis for emergence organismal complexity. To date, more than 650 types protein modifications, such as most well-known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short-chain long-chain acylation redox irreversible have been described, inventory is still increasing. By changing conformation, localization, activity, stability, charges, interactions with other biomolecules, PTMs ultimately alter phenotypes biological processes cells. The homeostasis important human health. Abnormal may cause changes in properties loss functions, are closely related occurrence development various diseases. In this review, we systematically introduce characteristics, regulatory mechanisms, functions health addition, therapeutic prospects diseases by targeting associated enzymes also summarized. This work will deepen understanding promote discovery diagnostic prognostic markers drug targets

Язык: Английский

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Exosomal circRNA: emerging insights into cancer progression and clinical application potential

Journal of Hematology & Oncology, Год журнала: 2023, Номер 16(1)

Опубликована: Июнь 26, 2023

Abstract Exosomal circRNA serves a novel genetic information molecule, facilitating communication between tumor cells and microenvironmental cells, such as immune fibroblasts, other components, thereby regulating critical aspects of cancer progression including escape, angiogenesis, metabolism, drug resistance, proliferation metastasis. Interestingly, microenvironment have new findings in influencing escape mediated by the release exosomal circRNA. Given intrinsic stability, abundance, broad distribution circRNAs, they represent excellent diagnostic prognostic biomarkers for liquid biopsy. Moreover, artificially synthesized circRNAs may open up possibilities therapy, potentially bolstered nanoparticles or plant exosome delivery strategies. In this review, we summarize functions underlying mechanisms cell non-tumor cell-derived progression, with special focus on their roles immunity metabolism. Finally, examine potential application therapeutic targets, highlighting promise clinical use.

Язык: Английский

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The role of AMPK in cancer metabolism and its impact on the immunomodulation of the tumor microenvironment

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Фев. 15, 2023

Adenosine monophosphate-activated protein kinase (AMPK) is a key metabolic sensor that pivotal for the maintenance of cellular energy homeostasis. AMPK contributes to diverse and physiological effects besides its fundamental role in glucose lipid metabolism. Aberrancy signaling one determining factors which lead development chronic diseases such as obesity, inflammation, diabetes, cancer. The activation downstream cascades orchestrate dynamic changes tumor bioenergetics. It well documented possesses suppressor context progression by modulating inflammatory pathways. In addition, plays central potentiating phenotypic functional reprogramming various classes immune cells reside microenvironment (TME). Furthermore, AMPK-mediated responses facilitate recruitment certain types TME, impedes development, progression, metastasis Thus, appears play an important regulation anti-tumor response regulating plasticity cells. effectuates modulation immunity via nutrient TME virtue molecular crosstalk with major checkpoints. Several studies including from our lab emphasize on anticancer several phytochemicals, are potential drug candidates. scope this review encompasses significance cancer metabolism influence drivers within special emphasis use phytochemicals target combat

Язык: Английский

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Cancer metabolites: promising biomarkers for cancer liquid biopsy

Biomarker Research, Год журнала: 2023, Номер 11(1)

Опубликована: Июнь 30, 2023

Abstract Cancer exerts a multitude of effects on metabolism, including the reprogramming cellular metabolic pathways and alterations in metabolites that facilitate inappropriate proliferation cancer cells adaptation to tumor microenvironment. There is growing body evidence suggesting aberrant play pivotal roles tumorigenesis metastasis, have potential serve as biomarkers for personalized therapy. Importantly, high-throughput metabolomics detection techniques machine learning approaches offer tremendous clinical oncology by enabling identification cancer-specific metabolites. Emerging research indicates circulating great promise noninvasive detection. Therefore, this review summarizes reported abnormal cancer-related last decade highlights application liquid biopsy, specimens, technologies, methods, challenges. The provides insights into promising tool applications.

Язык: Английский

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The role of AMPK in macrophage metabolism, function and polarisation

Journal of Translational Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Дек. 8, 2023

AMP-activated protein kinase (AMPK) is a ubiquitous sensor of energy and nutritional status in eukaryotic cells. It plays key role regulating cellular homeostasis multiple aspects cell metabolism. During macrophage polarisation, AMPK not only guides the metabolic programming macrophages, but also counter-regulates inflammatory function macrophages promotes their polarisation toward anti-inflammatory phenotype. located at intersection metabolism inflammation. The characteristics are closely related to immune-related diseases, infectious cancer progression immunotherapy. This review discusses structure its metabolism, macrophages. In addition, it summarises important pathway activators development macrophage-related diseases.

Язык: Английский

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PGAM1 Inhibition Promotes HCC Ferroptosis and Synergizes with Anti‐PD‐1 Immunotherapy

Advanced Science, Год журнала: 2023, Номер 10(29)

Опубликована: Сен. 14, 2023

Abstract The combination of immunotherapy and molecular targeted therapy exhibits promising therapeutic efficacy in hepatocellular carcinoma (HCC), but the underlying mechanism is still unclear. Here, phosphoglycerate mutase 1 (PGAM1) identified as a novel immunometabolic target by using bioinformatic algorithm based on multiple HCC datasets. PGAM1 highly expressed associated with poor prognosis response to immunotherapy. In vitro vivo experiments indicate that targeting inhibited cell growth promoted infiltration CD8 + T‐cells due decreased enzymatic activity. Mechanistically, inhibition promotes ferroptosis downregulating Lipocalin (LCN2) inducing energy stress ROS‐dependent AKT inhibition, which can also downregulate Programmed death 1‐ligand (PD‐L1). Moreover, an allosteric inhibitor (KH3) good antitumor effects patient‐derived xenograft (PDX) models enhanced anti‐PD‐1 subcutaneous orthotopic models. Taken together, findings demonstrate exerts effect promoting T‐cell synergize HCC. Targeting be new strategy “killing two birds one stone” for treatment.

Язык: Английский

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Tumor microenvironment as a complex milieu driving cancer progression: a mini review

Clinical & Translational Oncology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 28, 2024

Язык: Английский

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Tumor battlefield within inflamed, excluded or desert immune phenotypes: the mechanisms and strategies

Experimental Hematology and Oncology, Год журнала: 2024, Номер 13(1)

Опубликована: Авг. 6, 2024

Abstract The tumor microenvironment demonstrates great immunophenotypic heterogeneity, which has been leveraged in traditional immune-hot/cold categorization based on the abundance of intra-tumoral immune cells. By incorporating spatial contexture, immunophenotype was further elaborated into immune-inflamed, immune-excluded, and immune-desert. However, mechanisms underlying these different phenotypes are yet to be comprehensively elucidated. In this review, we discuss how cells interact collectively shape landscape from perspectives cells, extracellular matrix, cancer metabolism, summarize potential therapeutic options according distinct immunophenotypes for personalized precision medicine.

Язык: Английский

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Biodegradable Ferrous Sulfide-Based Nanocomposites for Tumor Theranostics through Specific Intratumoral Acidosis-Induced Metabolic Symbiosis Disruption

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(43), С. 19884 - 19895

Опубликована: Окт. 2, 2022

Abnormal metabolic symbiosis is a typical characteristic that differentiates the tumor regions from healthy tissues and meanwhile maintains survival. It of great potential to disrupt intratumoral in therapy. Herein, we report specific therapy strategy through inducing acidosis for elimination, which based on carbonic anhydrase inhibitor (CAI)-modified ferrous sulfide nanoparticles (FeS-PEG-CAI NPs). The FeS-PEG-CAI NPs show acid-responsive degradation capacity release functional components, including CAI, Fe2+, H2S, while remaining quite stable under normal physiological conditions. generated CAI H2S gas can not only intracellular induce but also provide suitable circumstances Fe2+-mediated Fenton reaction, producing abundant toxic hydroxyl radicals. Meanwhile, these dual-mode imaging with photoacoustic magnetic resonance imaging, dynamically monitor location process synergistic chemodynamic/photothermal/gas Overall, developed exert their role disrupting other effects, further enrich treatment strategies.

Язык: Английский

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