Metabolic adaptations in prostate cancer DOI Creative Commons

Mikel Pujana-Vaquerizo,

Laura Bozal-Basterra, Arkaitz Carracedo

et al.

British Journal of Cancer, Journal Year: 2024, Volume and Issue: 131(8), P. 1250 - 1262

Published: July 5, 2024

Prostate cancer is one of the most commonly diagnosed cancers in men and a major cause cancer-related deaths worldwide. Among molecular processes that contribute to this disease, weight metabolism has been placed under limelight recent years. Tumours exhibit metabolic adaptations comply with their biosynthetic needs. However, metabolites also play an important role supporting cell survival challenging environments or remodelling tumour microenvironment, thus being recognized as hallmark cancer. uniquely driven by androgen receptor signalling, knowledge influenced paths research. This review provides comprehensive perspective on support prostate progression beyond particular focus intrinsic extrinsic pathways.

Language: Английский

Ferroptosis: machinery and regulation DOI Open Access
Xin Chen, Jingbo Li, Rui Kang

et al.

Autophagy, Journal Year: 2020, Volume and Issue: 17(9), P. 2054 - 2081

Published: Aug. 19, 2020

Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death caused by lipid peroxidation, which controlled integrated oxidation and antioxidant systems. The iron-containing enzyme lipoxygenase the main promoter ferroptosis producing hydroperoxides, its function relies on activation ACSL4-dependent biosynthesis. In contrast, selenium-containing GPX4 currently recognized as a central repressor ferroptosis, activity depends glutathione produced from cystine-glutamate antiporter SLC7A11. Many metabolic (especially involving iron, lipids, amino acids) degradation pathways (macroautophagy/autophagy ubiquitin-proteasome system) orchestrate complex ferroptotic response through direct or indirect regulation iron accumulation peroxidation. Although detailed mechanism membrane injury during remains mystery, ESCRT III-mediated plasma repair can make cells resistant to ferroptosis. Here, we review recent rapid progress in understanding molecular mechanisms focus epigenetic, transcriptional, posttranslational this process.Abbreviations: 2ME: beta-mercaptoethanol; α-KG: α-ketoglutarate; ccRCC: clear renal carcinoma; EMT: epithelial-mesenchymal transition; FAO: fatty acid beta-oxidation; GSH: glutathione; MEFs: mouse embryonic fibroblasts; MUFAs: monounsaturated acids; NO: nitric oxide; NOX: NADPH oxidase; PPP: pentose phosphate pathway; PUFA: polyunsaturated acid; RCD: death; RNS: reactive nitrogen species; ROS: oxygen RTAs: radical-trapping antioxidants; UPS: system; UTR: untranslated region.

Language: Английский

Citations

1336
The Metabolic Underpinnings of Ferroptosis DOI Creative Commons
Jiashuo Zheng, Marcus Conrad

Cell Metabolism, Journal Year: 2020, Volume and Issue: 32(6), P. 920 - 937

Published: Nov. 20, 2020

Language: Английский

Citations

948
Ferroptosis at the intersection of lipid metabolism and cellular signaling DOI Creative Commons
Deguang Liang, Alexander M. Minikes, Xuejun Jiang

et al.

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(12), P. 2215 - 2227

Published: April 6, 2022

Language: Английский

Citations

628
Ferroptosis heterogeneity in triple-negative breast cancer reveals an innovative immunotherapy combination strategy DOI Creative Commons
Fan Yang, Yi Xiao, Jia-Han Ding

et al.

Cell Metabolism, Journal Year: 2022, Volume and Issue: 35(1), P. 84 - 100.e8

Published: Oct. 17, 2022

Treatment of triple-negative breast cancer (TNBC) remains challenging. Deciphering the orchestration metabolic pathways in regulating ferroptosis will provide new insights into TNBC therapeutic strategies. Here, we integrated multiomics data our large cohort (n = 465) to develop atlas. We discovered that TNBCs had heterogeneous phenotypes ferroptosis-related metabolites and pathways. The luminal androgen receptor (LAR) subtype was characterized by upregulation oxidized phosphatidylethanolamines glutathione metabolism (especially GPX4), which allowed utilization GPX4 inhibitors induce ferroptosis. Furthermore, verified inhibition not only induced tumor but also enhanced antitumor immunity. combination anti-PD1 possessed greater efficacy than monotherapy. Clinically, higher expression correlated with lower cytolytic scores worse prognosis immunotherapy cohorts. Collectively, this study demonstrated landscape revealed an innovative strategy for refractory LAR tumors.

Language: Английский

Citations

320
The cell biology of ferroptosis DOI
Scott J. Dixon, James A. Olzmann

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(6), P. 424 - 442

Published: Feb. 16, 2024

Language: Английский

Citations

271
Tumour fatty acid metabolism in the context of therapy resistance and obesity DOI
Andrew J. Hoy, Shilpa R. Nagarajan, Lisa M. Butler

et al.

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(12), P. 753 - 766

Published: Aug. 20, 2021

Language: Английский

Citations

259
The role of lipids in cancer progression and metastasis DOI Creative Commons
Miguel Martín‐Pérez,

Uxue Urdiroz-Urricelqui,

Claudia Bigas

et al.

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(11), P. 1675 - 1699

Published: Oct. 18, 2022

Language: Английский

Citations

251
Regulation of ferroptosis by lipid metabolism DOI Creative Commons

Lauren E. Pope,

Scott J. Dixon

Trends in Cell Biology, Journal Year: 2023, Volume and Issue: 33(12), P. 1077 - 1087

Published: July 3, 2023

Language: Английский

Citations

220
Human DECR1 is an androgen-repressed survival factor that regulates PUFA oxidation to protect prostate tumor cells from ferroptosis DOI Creative Commons
Zeyad D. Nassar, Chui Y. Mah, Jonas Dehairs

et al.

eLife, Journal Year: 2020, Volume and Issue: 9

Published: July 20, 2020

Fatty acid β-oxidation (FAO) is the main bioenergetic pathway in human prostate cancer (PCa) and a promising novel therapeutic vulnerability. Here we demonstrate efficacy of targeting FAO clinical tumors cultured ex vivo, identify DECR1, encoding rate-limiting enzyme for oxidation polyunsaturated fatty acids (PUFAs), as robustly overexpressed PCa tissues associated with shorter relapse-free survival. DECR1 negatively-regulated androgen receptor (AR) target gene and, therefore, may promote cell survival resistance to AR therapeutics. knockdown selectively inhibited PUFAs, proliferation migration cells, including treatment resistant lines, suppressed tumor metastasis mouse xenograft models. Mechanistically, caused cellular accumulation enhanced mitochondrial oxidative stress lipid peroxidation, induced ferroptosis. These findings implicate PUFA via an unexplored facet that promotes cells.

Language: Английский

Citations

147
The diversity and breadth of cancer cell fatty acid metabolism DOI Creative Commons
Shilpa R. Nagarajan, Lisa M. Butler, Andrew J. Hoy

et al.

Cancer & Metabolism, Journal Year: 2021, Volume and Issue: 9(1)

Published: Jan. 7, 2021

Tumor cellular metabolism exhibits distinguishing features that collectively enhance biomass synthesis while maintaining redox balance and homeostasis. These attributes reflect the complex interactions between cell-intrinsic factors such as genomic-transcriptomic regulation cell-extrinsic influences, including growth factor nutrient availability. Alongside glucose amino acid metabolism, fatty supports tumorigenesis disease progression through a range of processes membrane biosynthesis, energy storage production, generation signaling intermediates. Here, we highlight complexity in cancer, various inputs outputs intracellular free pool, numerous ways these pathways influence behavior.

Language: Английский

Citations

146