Hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survival

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 25, 2023

It is well known that solid hypoxic tumour cells oxidise glucose through glycolysis, and the end product of this pathway fermented into lactate which accumulates in microenvironment (TME). Initially, it was proclaimed cancer cannot use lactate; therefore, they dump TME subsequently augment acidity milieu. Furthermore, acts as a sink with stope variable amount different pathophysiological condition. Regardless pumped out within TME, disappears immediately still remains an unresolved puzzle. Recent findings have paved exploring main role acidosis TME. Cancer utilise de novo fatty acid synthesis to initiate angiogenesis invasiveness, also plays crucial suppression immunity. re-programme lipid biosynthetic develop metabolic symbiosis normoxic, moderately severely cells. For instance: enable synthesizing poly unsaturated acids (PUFA) oxygen scarcity secretes excess Lactate from taken up by normoxic whereas converted back PUFAs after sequence reactions then liberated be utilized Although much about these biological processes, exact molecular pathways are involved remain unclear. This review attempts understand exploited angiogenesis, immunity cause re-programming synthesis. will help researchers proper understanding associated bimodal regulations

Language: Английский

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Urinary volatile organic compounds for colorectal cancer screening: A systematic review and meta-analysis

European Journal of Cancer, Journal Year: 2023, Volume and Issue: 186, P. 69 - 82

Published: March 6, 2023

Language: Английский

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Molecular Spies in Action: Genetically Encoded Fluorescent Biosensors Light up Cellular Signals

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(22), P. 12573 - 12660

Published: Nov. 13, 2024

Cellular function is controlled through intricate networks of signals, which lead to the myriad pathways governing cell fate. Fluorescent biosensors have enabled study these signaling in living systems across temporal and spatial scales. Over years there has been an explosion number fluorescent biosensors, as they become available for numerous targets, utilized spectral space, suited various imaging techniques. To guide users this extensive biosensor landscape, we discuss critical aspects proteins consideration development, smart tagging strategies, historical recent types, grouped by target, with a focus on design applications sensors systems.

Language: Английский

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Why may citrate sodium significantly increase the effectiveness of transarterial chemoembolization in hepatocellular carcinoma?

Drug Resistance Updates, Journal Year: 2021, Volume and Issue: 59, P. 100790 - 100790

Published: Dec. 1, 2021

Language: Английский

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A “Weird” Mitochondrial Fatty Acid Oxidation as a Metabolic “Secret” of Cancer

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 38

Published: Feb. 8, 2022

Cancer metabolism is an extensively studied field since the discovery of Warburg effect about 100 years ago and continues to be increasingly intriguing enigmatic so far. It has become clear that glycolysis not only abnormally activated metabolic pathway in cancer cells, but same true for fatty acid synthesis (FAS) mevalonate pathway. In last decade, a lot data have been accumulated on pronounced mitochondrial oxidation (mFAO) many types cells. this article, we discuss how mFAO can escape normal regulation under certain conditions overactivated. Such abnormal activation β-oxidation also combined with mutations enzymes Krebs cycle are common cancer. If overactivated other conditions, such as dysfunctions electron transport complexes, and/or hypoxia, may alter redox state matrix. We propose idea altered inhibited at segments link citrate-malate shuttle instead cycle. call condition “β-oxidation shuttle”. unconventional mFAO, separate pathway, unexplored far source energy, well cataplerosis, leading biomass accumulation, accelerated oxygen consumption, ultimately proliferation. inefficient energy must consume significantly more per mole ATP produced when acetyl-CoA consuming pathways, FAS

Language: Английский

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Triterpenoid ursolic acid regulates the environmental carcinogen benzo[a]pyrene-driven epigenetic and metabolic alterations in SKH-1 hairless mice for skin cancer interception

Carcinogenesis, Journal Year: 2024, Volume and Issue: 45(5), P. 288 - 299

Published: March 11, 2024

Abstract Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental carcinogens accountable to developing skin cancers. Recently, we reported that exposure benzo[a]pyrene (B[a]P), a common PAH, causes epigenetic and metabolic alterations in the initiation, promotion progression of non-melanoma cancer (NMSC). As follow-up investigation, this study examines how dietary triterpenoid ursolic acid (UA) regulates B[a]P-driven pathways SKH-1 hairless mice. Our results show UA intercepts against B[a]P-induced tumorigenesis at different stages NMSC. Epigenomic cytosines followed by guanine residues (CpG) methyl-seq data showed diminished B[a]P-mediated differentially methylated regions (DMRs) profiles. Transcriptomic RNA-seq revealed revoked expressed genes (DEGs) cancer-related genes, such as leucine-rich repeat LGI family member 2 (Lgi2) kallikrein-related peptidase 13 (Klk13), indicating plays vital role gene regulation its potential consequences NMSC interception. Association analysis DEGs DMRs found mRNA expression KLK13 was correlated with promoter CpG methylation status early-stage comparison group, could regulate modulating an early stage The metabolomic alters B[a]P-regulated cancer-associated metabolisms like thiamin metabolism, ascorbate aldarate metabolism during initiation phase; pyruvate, citrate beta-alanine pathothenate coenzyme A (CoA) biosynthesis late phase. Taken together, reverses epigenetic, transcriptomic reprogramming, potentially contributing overall interception

Language: Английский

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Liver X Receptor Ligand GAC0001E5 Downregulates Antioxidant Capacity and ERBB2/HER2 Expression in HER2-Positive Breast Cancer Cells

Cancers, Journal Year: 2024, Volume and Issue: 16(9), P. 1651 - 1651

Published: April 25, 2024

The HER2-positive subtype accounts for approximately one-fifth of all breast cancers. Insensitivity and development acquired resistance to targeted therapies in some patients contribute their poor prognosis. HER2 overexpression is associated with metabolic reprogramming, facilitating cancer cell growth survival. Novel liver X receptor (LXR) ligand GAC0001E5 (1E5) has been shown inhibit proliferation by disrupting glutaminolysis inducing oxidative stress. In this study, cells were treated 1E5 determine potential inhibitory effects mechanisms action Similar previous observations other types, treatments inhibited LXR activity, expression, proliferation. Expression fatty acid synthesis genes, including synthase (FASN), was downregulated following treatment, results from co-treatment experiments an FASN inhibitor suggest that the same pathway 1E5. Treatments disrupted resulted increased Strikingly, transcript protein levels both significantly Taken together, these findings indicate therapeutic targeting reprogramming via modulation

Language: Английский

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Metabolic Reprogramming in Thyroid Cancer

Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 39(3), P. 425 - 444

Published: June 10, 2024

Thyroid cancer is a common endocrine malignancy with increasing incidence globally. Although most cases can be treated effectively, some are more aggressive and have higher risk of mortality. Inhibiting RET BRAF kinases has emerged as potential therapeutic strategy for the treatment thyroid cancer, particularly in advanced or disease. However, development resistance mechanisms may limit efficacy these kinase inhibitors. Therefore, developing precise strategies to target cell metabolism overcome critical area research advancing treatment. In field therapeutics, researchers explored combinatorial involving dual metabolic inhibition inhibitors combination targeted therapy, chemotherapy, immunotherapy challenge plasticity. This review highlights need new approaches discusses promising targeting cancer. It also challenges posed by plasticity effective explores advantages combined targeting.

Language: Английский

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Extracellular citrate and metabolic adaptations of cancer cells

Cancer and Metastasis Reviews, Journal Year: 2021, Volume and Issue: 40(4), P. 1073 - 1091

Published: Dec. 1, 2021

Abstract It is well established that cancer cells acquire energy via the Warburg effect and oxidative phosphorylation. Citrate considered to play a crucial role in metabolism by virtue of its production reverse Krebs cycle from glutamine. Here, we review evidence extracellular citrate one key metabolites metabolic pathways present cells. We different mechanisms which involved keeping redox balance respond need intracellular synthesis under conditions. In this context, further discuss hypothesis plays switching between phosphorylation while uptake enhances metastatic activities therapy resistance. also possibility organs rich such as liver, brain bones might form perfect niche for secondary tumour growth improve survival colonising Consistently, support provided cancer-associated senescent discussed. Finally, highlight on immune potential modulate biological functions pro- anti-tumour microenvironment. Collectively, intriguing supporting regulation overall activity.

Language: Английский

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ACLY inhibitors induce apoptosis and potentiate cytotoxic effects of sorafenib in thyroid cancer cells

Endocrine, Journal Year: 2022, Volume and Issue: 78(1), P. 85 - 94

Published: June 27, 2022

Language: Английский

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