What is cancer metabolism?

Cell, Год журнала: 2023, Номер 186(8), С. 1670 - 1688

Опубликована: Фев. 28, 2023

Язык: Английский

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Tumor microenvironment signaling and therapeutics in cancer progression

Cancer Communications, Год журнала: 2023, Номер 43(5), С. 525 - 561

Опубликована: Апрель 2, 2023

Abstract Tumor development and metastasis are facilitated by the complex interactions between cancer cells their microenvironment, which comprises stromal extracellular matrix (ECM) components, among other factors. Stromal can adopt new phenotypes to promote tumor cell invasion. A deep understanding of signaling pathways involved in cell‐to‐cell cell‐to‐ECM is needed design effective intervention strategies that might interrupt these interactions. In this review, we describe microenvironment (TME) components associated therapeutics. We discuss clinical advances prevalent newly discovered TME, immune checkpoints immunosuppressive chemokines, currently used inhibitors targeting pathways. These include both intrinsic non‐autonomous TME: protein kinase C (PKC) signaling, Notch, transforming growth factor (TGF‐β) Endoplasmic Reticulum (ER) stress response, lactate Metabolic reprogramming, cyclic GMP–AMP synthase (cGAS)–stimulator interferon genes (STING) Siglec also recent Programmed Cell Death Protein 1 (PD‐1), Cytotoxic T‐Lymphocyte Associated 4 (CTLA4), T‐cell immunoglobulin mucin‐3 (TIM‐3) Lymphocyte Activating Gene 3 (LAG3) checkpoint along with C‐C chemokine receptor (CCR4)‐ class chemokines 22 (CCL22)/ 17 (CCL17), type 2 (CCR2)‐ (C‐C motif) ligand (CCL2), 5 (CCR5)‐ (CCL3) axis TME. addition, review provides a holistic TME as three‐dimensional microfluidic models believed recapitulate original characteristics patient hence may be platform study mechanisms screen for various anti‐cancer therapies. further systemic influences gut microbiota reprogramming treatment response. Overall, comprehensive analysis diverse most critical highlighting newest preclinical studies underlying biology. highlight importance technologies microfluidics lab‐on‐chip research present an overview extrinsic factors, such inhabitant human microbiome, have potential modulate biology drug responses.

Язык: Английский

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Acetyl-CoA regulates lipid metabolism and histone acetylation modification in cancer

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2022, Номер 1878(1), С. 188837 - 188837

Опубликована: Ноя. 17, 2022

Язык: Английский

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Positive feedback regulation between glycolysis and histone lactylation drives oncogenesis in pancreatic ductal adenocarcinoma

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Май 6, 2024

Abstract Background Metabolic reprogramming and epigenetic alterations contribute to the aggressiveness of pancreatic ductal adenocarcinoma (PDAC). Lactate-dependent histone modification is a new type mark, which links glycolysis metabolite process lactylation. However, role lactylation in PDAC remains unclear. Methods The level was identified by western blot immunohistochemistry, its relationship with overall survival evaluated using Kaplan-Meier plot. participation growth progression confirmed through inhibition inhibitors or lactate dehydrogenase A ( LDHA ) knockdown both vitro vivo. potential writers erasers were functional experiments. target genes H3K18 (H3K18la) screened CUT&Tag RNA-seq analyses. candidate TTK protein kinase BUB1 mitotic checkpoint serine/threonine B BUB1B validated ChIP-qPCR, RT-qPCR Next, effects these two overexpression. interaction between Co-IP assay. Results Histone lactylation, especially H3K18la elevated PDAC, high associated poor prognosis. suppression glycolytic activity different kinds contributed anti-tumor E1A binding p300 (P300) deacetylase 2 writer eraser cells, respectively. enriched at promoters activated transcription regulators . Interestingly, could elevate expression P300 turn increased glycolysis. Moreover, phosphorylated tyrosine 239 (Y239) LDHA, subsequently upregulated levels. Conclusions glycolysis-H3K18la-TTK/BUB1B positive feedback loop exacerbates dysfunction PDAC. These findings delivered exploration significant inter-relationship metabolic regulation, might pave way toward novel treatment strategies therapy.

Язык: Английский

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Mendelian inheritance revisited: dominance and recessiveness in medical genetics

Nature Reviews Genetics, Год журнала: 2023, Номер 24(7), С. 442 - 463

Опубликована: Фев. 20, 2023

Язык: Английский

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Lactate activates trained immunity by fueling the tricarboxylic acid cycle and regulating histone lactylation

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 4, 2025

Trained immunity refers to the long-term memory of innate immune cells. However, little is known about how environmental nutrient availability influences trained immunity. This study finds that physiologic carbon sources impact glucose contribution tricarboxylic acid (TCA) cycle and enhance cytokine production monocytes. Our experiments demonstrate monocytes preferentially employe lactate over as a TCA substrate, metabolism required for cell responses bacterial fungal infection. Except cycle, endogenous or exogenous also supports by regulating histone lactylation. Further transcriptome analysis, ATAC-seq, CUT&Tag-seq chromatin accessibility in manner dependent Inhibiting lactate-dependent silencing dehydrogenase A (LDHA) impairs both fueled These findings suggest hub immunometabolic epigenetic programs

Язык: Английский

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LDHA promotes osteoblast differentiation through histone lactylation

Biochemical and Biophysical Research Communications, Год журнала: 2022, Номер 615, С. 31 - 35

Опубликована: Май 13, 2022

Язык: Английский

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Metabolic enzyme LDHA activates Rac1 GTPase as a noncanonical mechanism to promote cancer

Nature Metabolism, Год журнала: 2022, Номер 4(12), С. 1830 - 1846

Опубликована: Дек. 19, 2022

Язык: Английский

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Moonlighting enzymes: when cellular context defines specificity

Cellular and Molecular Life Sciences, Год журнала: 2023, Номер 80(5)

Опубликована: Апрель 24, 2023

Язык: Английский

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Targeting acetyl-CoA carboxylase 1 for cancer therapy

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Фев. 10, 2023

Metabolic adaptation is an emerging hallmark of tumors. De novo fatty acid synthesis important metabolic process to produce intermediates for energy storage, biosynthesis membrane lipids and generation signaling molecules. Acetyl-CoA carboxylase 1 (ACC1) a critical enzyme in the synthesis, which carboxylates acetyl-CoA carboxylic form malonyl-CoA. The role makes it promising therapeutic target various diseases such as non-alcoholic liver disease, obesity diabetes. Tumors have high flow strong dependence on synthesis. Thus, inhibition has become potential choice anti-tumor therapy. In this review, we first introduced structure expression pattern 1. We also discussed molecular mechanisms initiation progression cancer types. Furthermore, carboxylase1 inhibitors been discussed. Collectively, summarized interplay between tumorigenesis, indicating tumor management.

Язык: Английский

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