Targeting ACSLs to modulate ferroptosis and cancer immunity

Trends in Endocrinology and Metabolism, Год журнала: 2024, Номер unknown

Опубликована: Окт. 1, 2024

Язык: Английский

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SLC35C2 promotes stemness and progression in hepatocellular carcinoma by activating lipogenesis

Cellular Signalling, Год журнала: 2025, Номер 127, С. 111589 - 111589

Опубликована: Янв. 5, 2025

Язык: Английский

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Transcription factor specificity protein (SP) family in renal physiology and diseases

PeerJ, Год журнала: 2025, Номер 13, С. e18820 - e18820

Опубликована: Янв. 20, 2025

Dysregulated specificity proteins (SPs), members of the C2H2 zinc-finger family, are crucial transcription factors (TFs) with implications for renal physiology and diseases. This comprehensive review focuses on role SP family members, particularly SP1 SP3, in pathology. A detailed analysis their expression cellular localization healthy human kidney is presented, highlighting involvement fatty acid metabolism, electrolyte regulation, synthesis important molecules. The also delves into diverse roles SPs various diseases, including ischemia/reperfusion injury, diabetic nephropathy, interstitial fibrosis, lupus nephritis, elucidating molecular mechanisms potential as therapeutic targets. further discusses pharmacological modulation its treatment. Our findings provide a understanding health disease, offering new avenues targeted interventions precision medicine nephrology.

Язык: Английский

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The prognostic role of ACSL4 in postoperative adjuvant TACE-treated HCC: implications for therapeutic response and mechanistic insights

Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)

Опубликована: Ноя. 19, 2024

Abstract Background The response of hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE) treatment and its underlying mechanisms remain elusive. This study investigates the role enzymes involved in fatty acid activation, specifically Acyl-CoA synthetase long chain 4 (ACSL4), HCC patients treated with postoperative adjuvant TACE (PA-TACE) nutrient-deprived cells. Methods We examined expression ACSL4 family members clinical samples cell lines. significance ACSL4, particularly regarding prognosis PA-TACE, was assessed using two independent cohorts. further explored glucose starvation-induced death cells xenograft mouse models. Results Among members, is most up-regulated enzyme, associated poor survival patients, post-recurrent TACE-treated a Singapore cohort. essential for starvation, rather than hypoxia or combination doxorubicin cisplatin. ACSL4-mediated arachidonic (AA) metabolism supports mitochondrial β -oxidation energy production. CCAAT/enhancer binding protein α (CEBPA) transcriptionally regulates by 3 motifs (-623 -613, -1197 -1187 -1745 -1735) upstream promoter region, enhancing pro-survival effects. Furthermore, canagliflozin (Cana), clinical-approved drug type 2 diabetes, mimics starvation inhibits growth ACSL4-low tumors. Moreover, high CEBPA expressions correlate increased recurrence susceptibility after PA-TACE China-Guangxi Conclusions CEBPA-ACSL4 pathway critical protecting from death, suggesting that could serve as valuable prognostic indicators potential therapeutic targets context HCC. Graphical first-line intermediate-stage unresectable tumor common (PA) treatment. present found presence are more resistant TACE, susceptible relapse poorer survival. Mechanically, activation conversion into AA-CoA, which promotes lipid anabolism nutrition-replete condition catabolism glucose-deplete condition. As result, ACSL4-high cells, restriction (rather chemotherapeutic drugs), can donor production through protect membrane impairment vitro vivo . In addition, activates , knockout aborted metabolism.

Язык: Английский

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Regulation of Cancer Metastasis by PAK2

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(24), С. 13443 - 13443

Опубликована: Дек. 15, 2024

PAK2 is a serine-threonine kinase and member of the p21-activated (PAK) family. activated by GTP-bound rho family GTPases, Rac, Cdc42, it regulates actin dynamics, cell adhesion to extracellular matrix, motility. In various types cancers, has been implicated in regulation cancer proliferation, cycle, apoptosis. addition, recent studies have shown that plays an important role metastasis, indicating as potential therapeutic target. This review discusses discoveries on functions cancers. A better understanding mechanisms function will facilitate future development therapies.

Язык: Английский

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PAK2 as a therapeutic target in cancer: Mechanisms, challenges, and future perspectives

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2024, Номер 1880(1), С. 189246 - 189246

Опубликована: Дек. 16, 2024

Язык: Английский

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Investigating the hub genes and genetic basis regulating fatty acid metabolictraits in chicken breast muscle based on combined genomic and transcriptomic approaches

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Сен. 2, 2024

Background The composition of various fatty acids in meat plays a crucial role the evaluation nutritional indicators poultry and human health. Fatty acid metabolic can more accurately reflect status its acceptance by general public. In this study, we utilized two analytical approaches, Genome-Wide Association Study (GWAS) Weighted Gene Co-expression Network Analysis (WGCNA), to elucidate genetic mechanisms underlying traits chicken breast muscle.Initially, GWAS was conducted based on genotype data obtained genotyping sequencing (GBS) from 415 chickens Gushi-Anka F2 resource population phenotypic 33 metabolism muscle. Results We identified total 291 significant single nucleotide polymorphisms (SNPs) associated with content 12 types such as C14:0/C12:0, C18:0/C16:0, C18:1/C18:0, etc., which were mapped chromosomes (Chr) 1, 2, 3, 4, 5, 7, 9, 10. The most SNP Chr2:102, 676, 165 (P = 1.20E-06), explained 2.33% variation polyunsaturated (PUFA)/mono-unsaturated (MUFA) synthesis pathway. that highest Chr4: 30, 150, 765 (5.85%). Interestingly, signals for three (C22:4/C18:3, C20:3/C18:3, C22:6/C18:3) within same gene interval Chr 9 (Chr9: 5.75 - 8.99Mb). Concurrently, WGCNA using 613 candidate genes linkage disequilibrium regions aforementioned SNPs, well transcriptome values muscle Gujshi periods, 13 hub (FIG4, METTL4, PLD4, IDH1, FH, SDHA, EHHADH, AKT1, PIK3CB, LPIN2, FUT9, PAK2, ACSL3) finally determined. Further, constructed functional networks involving these deduced potential Conclusion These results enhance our understanding regulation muscle, providing theoretical basis future breeding practices targeting traits.

Язык: Английский

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[Ferroptosis inducer Erastin inhibits proliferation of liver cancer cells

PubMed, Год журнала: 2024, Номер 44(11), С. 2131 - 2136

Опубликована: Ноя. 20, 2024

To investigate the expression of Acyl-CoA synthetase long-chain family member 4 (ACSL4) in liver cancer and its role regulating ferroptosis proliferation cells.

Язык: Английский

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