The function of lactate dehydrogenase A in retinal neurons: implications to retinal degenerative diseases DOI Creative Commons

Ammaji Rajala,

Mohd Akbar Bhat, Kenneth Teel

et al.

PNAS Nexus, Journal Year: 2023, Volume and Issue: 2(3)

Published: Feb. 3, 2023

Abstract The postmitotic retina is highly metabolic and the photoreceptors depend on aerobic glycolysis for an energy source cellular anabolic activities. Lactate dehydrogenase A (LDHA) a key enzyme in glycolysis, which converts pyruvate to lactate. Here we show that cell-type-specific actively translating mRNA purification by ribosome affinity shows predominant expression of LDHA rods cones LDHB retinal pigment epithelium Müller cells. We genetic ablation resulted diminished visual function, loss structure, dorsal–ventral patterning cone-opsin gradient. Loss increased glucose availability, promoted oxidative phosphorylation, upregulated glutamine synthetase (GS), neuron survival factor. However, lacking cells does not affect function mice. Glucose shortage associated with diseases, such as age-related macular degeneration (AMD), regulating levels may have therapeutic relevance. These data demonstrate unique unexplored roles maintenance healthy retina.

Language: Английский

Tumor glycolysis, an essential sweet tooth of tumor cells DOI
Sumana Paul, Saikat Ghosh, Sushil Kumar

et al.

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 86, P. 1216 - 1230

Published: Oct. 28, 2022

Language: Английский

Citations

192
Lactate Rewires Lipid Metabolism and Sustains a Metabolic–Epigenetic Axis in Prostate Cancer DOI Open Access
Luigi Ippolito, Giuseppina Comito, Matteo Parri

et al.

Cancer Research, Journal Year: 2022, Volume and Issue: 82(7), P. 1267 - 1282

Published: Feb. 8, 2022

Abstract Lactate is an abundant oncometabolite in the tumor environment. In prostate cancer, cancer-associated fibroblasts (CAF) are major contributors of secreted lactate, which can be taken up by cancer cells to sustain mitochondrial metabolism. However, how lactate impacts transcriptional regulation tumors has yet fully elucidated. Here, we describe a mechanism CAF-secreted able increase expression genes involved lipid metabolism cells. This enhanced intracellular accumulation droplets (LD) and provided acetyl moieties for histone acetylation, establishing regulatory loop between metabolites epigenetic modification. Inhibition this targeting bromodomain extraterminal protein family acetylation readers suppressed perilipin 2 (PLIN2), crucial component LDs, disrupting lactate-dependent metabolic rewiring. CAF-induced metabolic–epigenetic vivo reduced growth metastasis cells, demonstrating its translational relevance as therapeutic target cancer. Clinically, PLIN2 was elevated with higher Gleason grade castration-resistant compared primary Overall, these findings show that both role promoting progression. Significance: work shows stromal-derived induces droplets, stimulates rewiring, fosters metastatic potential

Language: Английский

Citations

104
Metabolic reprogramming and epigenetic modifications in cancer: from the impacts and mechanisms to the treatment potential DOI Creative Commons
Xuemeng Xu, Peng Qiu,

Xianjie Jiang

et al.

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(7), P. 1357 - 1370

Published: July 3, 2023

Abstract Metabolic reprogramming and epigenetic modifications are hallmarks of cancer cells. In cells, metabolic pathway activity varies during tumorigenesis progression, indicating regulated plasticity. changes often closely related to changes, such as alterations in the expression or epigenetically modified enzymes, which may exert a direct an indirect influence on cellular metabolism. Therefore, exploring mechanisms underlying regulating tumor cell metabolism is important for further understanding pathogenesis. Here, we mainly focus latest studies regulations, including glucose, lipid amino acid context, then emphasize modifications. Specifically, discuss role played by DNA methylation, chromatin remodeling, noncoding RNAs histone lactylation growth progression. Finally, summarize prospects potential therapeutic strategies based

Language: Английский

Citations

97
Glutamine addiction in tumor cell: oncogene regulation and clinical treatment DOI Creative Commons
Xian Li, Xueqiang Peng, Yan Li

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 3, 2024

Abstract After undergoing metabolic reprogramming, tumor cells consume additional glutamine to produce amino acids, nucleotides, fatty and other substances facilitate their unlimited proliferation. As such, the metabolism of is intricately linked survival progression cancer cells. Consequently, targeting presents a promising strategy inhibit growth cell development. This review describes uptake, metabolism, transport in its pivotal role biosynthesis more. Furthermore, we have also summarized impact oncogenes like C-MYC , KRAS HIF p53 on regulation mechanisms through which triggers mTORC1 activation. In addition, different anti-cancer agents has been described prospective applications are assessed.

Language: Английский

Citations

23
Molecular landmarks of tumor disulfidptosis across cancer types to promote disulfidptosis-target therapy DOI Creative Commons
Deze Zhao,

Yu Meng,

Yating Dian

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 68, P. 102966 - 102966

Published: Nov. 19, 2023

The mystery about the mechanistic basis of disulfidptosis has recently been unraveled and shows promise as an effective treatment modality for triggering cancer cell death. However, limited understanding role in tumor progression drug sensitivity hindered development disulfidptosis-targeted therapy combinations with other therapeutic strategies. Here, we established a signature model to estimate status approximately 10,000 samples across 33 types revealed its prognostic value. Then, characterized disulfidptosis-associated molecular features identified various alterations that correlate both drug-resistant drug-sensitive responses anti-tumor drugs. We further showed vast heterogeneity among 760 lines 25 types. experimentally validated score-high are more susceptible glucose starvation-induced compared their counterparts low scores. Finally, investigated impact on response induction may enhance anti-cancer drugs, but some cases, it could also lead resistance cultured cells. Overall, our multi-omics analysis firstly elucidates comprehensive profile disulfidptosis-related alterations, prognosis, potential therapies at pan-cancer level. These findings uncover opportunities utilize multiple sensitivities induced by disulfidptosis, thereby offering practical implications clinical therapy.

Language: Английский

Citations

25
Tumor lactic acid: a potential target for cancer therapy DOI
Jun‐Kyu Byun

Archives of Pharmacal Research, Journal Year: 2023, Volume and Issue: 46(2), P. 90 - 110

Published: Feb. 1, 2023

Language: Английский

Citations

23
Lactate enhances NMNAT1 lactylation to sustain nuclear NAD+ salvage pathway and promote survival of pancreatic adenocarcinoma cells under glucose-deprived conditions DOI
Huimin Huang, Shitong Wang, Hongping Xia

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 588, P. 216806 - 216806

Published: March 11, 2024

Language: Английский

Citations

12
Site-specific controlled-release nanoparticles for immune reprogramming via dual metabolic inhibition against triple-negative breast cancer DOI

Wenyan She,

Haimei Li, Zichen Wang

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 366, P. 204 - 220

Published: Jan. 3, 2024

Language: Английский

Citations

10
The Cancer Antioxidant Regulation System in Therapeutic Resistance DOI Creative Commons

Xuanhao Gu,

Chunyang Mu,

Rujia Zheng

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(7), P. 778 - 778

Published: June 27, 2024

Antioxidants play a pivotal role in neutralizing reactive oxygen species (ROS), which are known to induce oxidative stress. In the context of cancer development, cells adeptly maintain elevated levels both ROS and antioxidants through process termed "redox reprogramming". This balance optimizes proliferative influence while simultaneously reducing potential for cause damage cell. some cases, adapted antioxidant machinery can hamper efficacy treatments neoplastic diseases, representing significant facet resistance mechanisms observed therapy. this review, we outline contribution systems therapeutic resistance. We detail fundamental constituents these systems, encompassing central regulatory involving transcription factors (of particular importance is KEAP1/NRF2 signaling axis), molecular effectors antioxidants, auxiliary responsible NADPH generation. Furthermore, present recent clinical trials based on targeted treatment cancer, assessing as well challenges strategy Additionally, summarize pressing issues field, with aim illuminating path toward emergence novel anticancer approaches by orchestrating redox signaling.

Language: Английский

Citations

10
The Tricarboxylic Acid Cycle Metabolites for Cancer: Friend or Enemy DOI Creative Commons
Jie Wu, Nian Liu, Jing Chen

et al.

Research, Journal Year: 2024, Volume and Issue: 7

Published: Jan. 1, 2024

The tricarboxylic acid (TCA) cycle is capable of providing sufficient energy for the physiological activities under aerobic conditions. Although tumor metabolic reprogramming places glycolysis in a dominant position, TCA remains indispensable cells as hub linkage and interconversion glucose, lipids, certain amino acids. intermediates such citrate, α-ketoglutarate, succinate, fumarate are altered tumors, they regulate metabolism, signal transduction, immune environment to affect tumorigenesis progression. This article provides comprehensive review modifications occurring relation cycle, which affects pathogenesis current therapeutic strategy therapy through targeting cancer cells.

Language: Английский

Citations

9