Mitochondrial Alterations in Prostate Cancer: Roles in Pathobiology and Racial Disparities DOI Open Access
Kunwar Somesh Vikramdeo,

Amod Sharma,

Shashi Anand

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4482 - 4482

Published: Feb. 24, 2023

Prostate cancer (PCa) affects millions of men worldwide and is a major cause cancer-related mortality. Race-associated PCa health disparities are also common both social clinical concern. Most diagnosed early due to PSA-based screening, but it fails discern between indolent aggressive PCa. Androgen or androgen receptor-targeted therapies standard care treatment for locally advanced metastatic disease, therapy resistance common. Mitochondria, the powerhouse cells, unique subcellular organelles that have their own genome. A large majority mitochondrial proteins are, however, nuclear-encoded imported after cytoplasmic translation. Mitochondrial alterations in cancer, including PCa, leading altered functions. Aberrant function nuclear gene expression retrograde signaling promotes tumor-supportive stromal remodeling. In this article, we discuss been reported review literature related roles pathobiology, resistance, racial disparities. We translational potential as prognostic biomarkers effective targets therapy.

Language: Английский

Arginine Signaling and Cancer Metabolism DOI Open Access
Chia‐Lin Chen, Sheng-Chieh Hsu, David K. Ann

et al.

Cancers, Journal Year: 2021, Volume and Issue: 13(14), P. 3541 - 3541

Published: July 15, 2021

Arginine is an amino acid critically involved in multiple cellular processes including the syntheses of nitric oxide and polyamines, a direct activator mTOR, nutrient-sensing kinase strongly implicated carcinogenesis. Yet, it also considered as non- or semi-essential acid, due to normal cells’ intrinsic ability synthesize arginine from citrulline aspartate via ASS1 (argininosuccinate synthase 1) ASL lyase). As such, can be used dietary supplement its depletion therapeutic strategy. Strikingly, over 70% tumors, transcription suppressed, rendering cells addicted external arginine, forming basis arginine-deprivation therapy. In this review, we will discuss signaling metabolite, arginine’s role cancer metabolism, epigenetic regulator, immunomodulator, target. We provide comprehensive summary ADI (arginine deiminase)-based preclinical studies update clinical trials for arginase. The different cell killing mechanisms associated with various types described.

Language: Английский

Citations

169
Spatially resolved multi-omics highlights cell-specific metabolic remodeling and interactions in gastric cancer DOI Creative Commons
Chenglong Sun, Anqiang Wang, Yanhe Zhou

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 10, 2023

Abstract Mapping tumor metabolic remodeling and their spatial crosstalk with surrounding non-tumor cells can fundamentally improve our understanding of biology, facilitates the designing advanced therapeutic strategies. Here, we present an integration mass spectrometry imaging-based metabolomics lipidomics microarray-based transcriptomics to hierarchically visualize intratumor heterogeneity cell interactions in same gastric cancer sample. Tumor-associated reprogramming is imaged at metabolic-transcriptional levels, maker metabolites, lipids, genes are connected pathways colocalized heterogeneous tissues. Integrated data from multi-omics approaches coherently identify types distributions within complex microenvironment, immune cell-dominated “tumor-normal interface” region where contact adjacent tissues characterized distinct transcriptional signatures significant immunometabolic alterations. Our approach for mapping tissue molecular architecture provides highly integrated picture heterogeneity, transform metabolism systemic level.

Language: Английский

Citations

138
Arginine reprograms metabolism in liver cancer via RBM39 DOI Creative Commons
Dirk Mossmann, Christoph Müller, Sujin Park

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(23), P. 5068 - 5083.e23

Published: Oct. 6, 2023

Metabolic reprogramming is a hallmark of cancer. However, mechanisms underlying metabolic and how altered metabolism in turn enhances tumorigenicity are poorly understood. Here, we report that arginine levels elevated murine patient hepatocellular carcinoma (HCC), despite reduced expression synthesis genes. Tumor cells accumulate high due to increased uptake arginine-to-polyamine conversion. Importantly, the promote tumor formation via further reprogramming, including changes glucose, amino acid, nucleotide, fatty acid metabolism. Mechanistically, binds RNA-binding motif protein 39 (RBM39) control RBM39-mediated upregulation asparagine leads enhanced uptake, creating positive feedback loop sustain oncogenic Thus, second messenger-like molecule reprograms growth.

Language: Английский

Citations

113
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

96
Detection of early seeding of Richter transformation in chronic lymphocytic leukemia DOI Creative Commons
Ferran Nadeu, Romina Royo, Ramon Massoni-Badosa

et al.

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(8), P. 1662 - 1671

Published: Aug. 1, 2022

Abstract Richter transformation (RT) is a paradigmatic evolution of chronic lymphocytic leukemia (CLL) into very aggressive large B cell lymphoma conferring dismal prognosis. The mechanisms driving RT remain largely unknown. We characterized the whole genome, epigenome and transcriptome, combined with single-cell DNA/RNA-sequencing analyses functional experiments, 19 cases CLL developing RT. Studying 54 longitudinal samples covering up to years disease course, we uncovered minute subclones carrying genomic, immunogenetic transcriptomic features cells already at diagnosis, which were dormant for before transformation. also identified new driver alterations, discovered mutational signature (SBS-RT), recognized an oxidative phosphorylation (OXPHOS) high –B receptor (BCR) low -signaling transcriptional axis in showed that OXPHOS inhibition reduces proliferation cells. These findings demonstrate early seeding advanced stages cancer uncover potential therapeutic targets

Language: Английский

Citations

91
Arginine and Arginases Modulate Metabolism, Tumor Microenvironment and Prostate Cancer Progression DOI Open Access
Andreia Matos,

Marcos Carvalho,

Manuel Bicho

et al.

Nutrients, Journal Year: 2021, Volume and Issue: 13(12), P. 4503 - 4503

Published: Dec. 16, 2021

Arginine availability and activation of arginine-related pathways at cancer sites have profound effects on the tumor microenvironment, far beyond their well-known role in hepatic urea cycle. metabolism impacts not only malignant cells but also surrounding immune behavior, modulating growth, survival, immunosurveillance mechanisms, either through an arginase-mediated effect polyamines proline synthesis, or by arginine/nitric oxide pathway cells, antitumor T-cells, myeloid-derived suppressor macrophages. This review presents evidence concerning impact arginine arginase activity prostate highlighting recent advances immunotherapy, which might be relevant for cancer. Even though further research is required, deprivation may represent a novel antimetabolite strategy treatment arginine-dependent

Language: Английский

Citations

62
The Hippo Pathway Effectors YAP/TAZ-TEAD Oncoproteins as Emerging Therapeutic Targets in the Tumor Microenvironment DOI Open Access

Reza Bayat Mokhtari,

Neda Ashayeri,

Leili Baghaie

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(13), P. 3468 - 3468

Published: July 2, 2023

Various cancer cell-associated intrinsic and extrinsic inputs act on YAP/TAZ proteins to mediate the hyperactivation of TEAD transcription factor-based transcriptome. This YAP/TAZ-TEAD activity can override growth-limiting Hippo tumor-suppressor pathway that maintains normal tissue homeostasis. Herein, we provide an integrated summary contrasting roles during homeostasis versus tumor initiation progression. In addition upstream factors regulate in TME, critical insights emerging functions immune suppression abnormal vasculature development tumorigenesis are illustrated. Lastly, discuss current methods intervene with oncogenic signaling applications combination therapies, gut microbiota, epigenetic plasticity could potentiate efficacy chemo/immunotherapy as improved therapeutic strategies.

Language: Английский

Citations

34
Crosstalk between oxidative phosphorylation and immune escape in cancer: a new concept of therapeutic targets selection DOI

Xutong Qiu,

Yi Li, Zhuoyuan Zhang

et al.

Cellular Oncology, Journal Year: 2023, Volume and Issue: 46(4), P. 847 - 865

Published: April 11, 2023

Language: Английский

Citations

28
Engineered bacteria in tumor immunotherapy DOI
Hua Chen,

Yinrui Zhu,

Chonghai Zhang

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 589, P. 216817 - 216817

Published: March 15, 2024

Language: Английский

Citations

11
Arginine Metabolism Reprogramming in Perfluorooctanoic Acid (PFOA)-Induced Liver Injury DOI
Jie Gao, Tiantian Li, Wei Guo

et al.

Environmental Science & Technology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Perfluorooctanoic acid (PFOA) is a persistent pollutant that has gained worldwide attention, owing to its widespread presence in the environment. Previous studies have reported PFOA upregulates lipid metabolism and associated with liver injury humans. However, when fatty degradation pathway activated, accumulation still occurs, suggesting of unknown pathways mechanisms remain be elucidated. In this study, adult C57BL/6N mice were exposed at 0.1, 1, 10 mg/kg/day. Using integrated metabolomics transcriptomics, it was uncovered arginine differentially downregulated all three groups. vitro confirmed downregulation MIHA cell lines treated PFOA. Supplementation could effectively rescue downregulate chemokine levels caused by This finding highlights contribution maintaining health following exposure suggests potential metabolic immune modulation.

Language: Английский

Citations

1