Histone lactylation dynamics: Unlocking the triad of metabolism, epigenetics, and immune regulation in metastatic cascade of pancreatic cancer DOI Creative Commons
Xing Wang, Xiaohong Liu, Ruiling Xiao

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 598, P. 217117 - 217117

Published: July 15, 2024

Cancer cells rewire metabolism to sculpt the immune tumor microenvironment (TME) and propel advancement, which intricately tied post-translational modifications. Histone lactylation has emerged as a novel player in modulating protein functions, whereas little is known about its pathological role pancreatic ductal adenocarcinoma (PDAC) progression. Employing multi-omics approach encompassing bulk single-cell RNA sequencing, metabolomics, ATAC-seq, CUT&Tag methodologies, we unveiled potential of histone prognostic prediction, patient stratification TME characterization. Notably, "LDHA-H4K12la-immuno-genes" axis introduced node into regulatory framework "metabolism-epigenetics-immunity," shedding new light on landscape PDAC Furthermore, heightened interplay between cancer counterparts via Nectin-2 liver metastasis with elevated HLS unraveled positive feedback loop driving evasion. Simultaneously, exhibited altered autonomous functionality across metastatic cascade. Consequently, exploration innovative combination strategies targeting metabolism-epigenetics-immunity holds promise curbing distant improving survival prospects for individuals grappling challenges PDAC.

Language: Английский

The hallmarks of cancer immune evasion DOI
Claudia Galassi, Timothy A. Chan, Ilio Vitale

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(11), P. 1825 - 1863

Published: Oct. 10, 2024

Language: Английский

Citations

70
Dubosiella newyorkensis modulates immune tolerance in colitis via the L-lysine-activated AhR-IDO1-Kyn pathway DOI Creative Commons

Yanan Zhang,

Shuyu Tu,

Xingwei Ji

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 13, 2024

Abstract Commensal bacteria generate immensely diverse active metabolites to maintain gut homeostasis, however their fundamental role in establishing an immunotolerogenic microenvironment the intestinal tract remains obscure. Here, we demonstrate that understudied murine commensal bacterium, Dubosiella newyorkensis , and its human homologue Clostridium innocuum have a probiotic immunomodulatory effect on dextran sulfate sodium-induced colitis using conventional, antibiotic-treated germ-free mouse models. We identify important for D. rebalancing Treg/Th17 responses ameliorating mucosal barrier injury by producing short-chain fatty acids, especially propionate L-Lysine (Lys). further show Lys induces immune tolerance ability of dendritic cells (DCs) enhancing Trp catabolism towards kynurenine (Kyn) pathway through activation metabolic enzyme indoleamine-2,3-dioxygenase 1 (IDO1) aryl hydrocarbon receptor (AhR)-dependent manner. This study identifies previously unrecognized communication which Lys-producing exert immunoregulatory capacity establish Treg-mediated immunosuppressive activating AhR-IDO1-Kyn circuitry DCs. circuit represents potential therapeutic target treatment inflammatory bowel diseases.

Language: Английский

Citations

65
Hallmarks of cancer stemness DOI Creative Commons

Jia-Jian Loh,

Stephanie Ma

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(5), P. 617 - 639

Published: May 1, 2024

Language: Английский

Citations

63
Cancer cell metabolism and antitumour immunity DOI
Mara De Martino, Jeffrey C. Rathmell, Lorenzo Galluzzi

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 24(9), P. 654 - 669

Published: April 22, 2024

Language: Английский

Citations

54
Lysine lactylation in the regulation of tumor biology DOI
Zijian Yang,

Yingqi Zheng,

Qiang Gao

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(8), P. 720 - 731

Published: Feb. 22, 2024

Language: Английский

Citations

28
Glutaryl-CoA dehydrogenase suppresses tumor progression and shapes an anti-tumor microenvironment in hepatocellular carcinoma DOI

Yuanxiang Lao,

Xiaohan Cui, Zhu Xu

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 81(5), P. 847 - 861

Published: June 1, 2024

Language: Английский

Citations

18
Crossing epigenetic frontiers: the intersection of novel histone modifications and diseases DOI Creative Commons

Weiyi Yao,

Xinting Hu,

Xin Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 16, 2024

Abstract Histone post-translational modifications (HPTMs), as one of the core mechanisms epigenetic regulation, are garnering increasing attention due to their close association with onset and progression diseases potential targeted therapeutic agents. Advances in high-throughput molecular tools abundance bioinformatics data have led discovery novel HPTMs which similarly affect gene expression, metabolism, chromatin structure. Furthermore, a growing body research has demonstrated that histone also play crucial roles development various diseases, including cancers, cardiovascular infectious psychiatric disorders, reproductive system diseases. This review defines nine modifications: lactylation, citrullination, crotonylation, succinylation, SUMOylation, propionylation, butyrylation, 2-hydroxyisobutyrylation, 2-hydroxybutyrylation. It comprehensively introduces modification processes these HPTMs, transcription, replication, DNA repair recombination, structure, well involvement promoting occurrence clinical applications targets biomarkers. Moreover, this provides detailed overview HPTM inhibitors targeting emerging strategies treatment multiple while offering insights into future prospects challenges. Additionally, we briefly introduce techniques field research.

Language: Английский

Citations

18
Salicylic acid enhances cell growth, fatty acid and astaxanthin production in heterotrophic Chromochloris zofingiensis without reactive oxygen species elevation DOI Creative Commons
Xinwei Zhang, Zhao Zhang, Yanmei Peng

et al.

Biotechnology for Biofuels and Bioproducts, Journal Year: 2024, Volume and Issue: 17(1)

Published: Jan. 3, 2024

Abstract Background The induction of lipid and astaxanthin accumulation in microalgae is often achieved through abiotic stress. However, this approach usually leads to oxidative stress, which results relatively low growth rate. Phytohormones, as important small molecule signaling substances, not only affect the metabolism but also influence intracellular reactive oxygen species level. This study aimed screen phytohormones that could promote fatty acids yield heterotrophic Chromochloris zofingiensis without causing damage, further investigate underlying mechanisms. Results In present study, among all selected phytohormones, addition exogenous salicylic acid (SA) effectively cell along with total (TFA) C. . Notably, highest yields TFA were at 100 μM SA, 43% 97.2% higher compared control, respectively. Interestingly, (ROS) levels, are increased elevated content under stresses, significantly decreased by SA treatment. Comparative transcriptome analysis unveiled significant alterations overall carbon SA. Specifically, upregulation synthesis pathway, β-carotene-4-ketolase (BKT) carotenoid aligned biochemical findings. Weighted gene co-expression network highlighted ABC transporters GTF2B-like transcription factor potential key regulators. Conclusion found can serve an effective regulator celling ROS elevation, provides a promising for production inhibition. Graphical

Language: Английский

Citations

17
VEGFR3 mitigates hypertensive nephropathy by enhancing mitophagy via regulating crotonylation of HSPA1L DOI Creative Commons
Q Wu,

Jiaxin Fu,

Bin Zhu

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 28, 2025

Oxidative stress-associated proximal tubular cells (PTCs) damage is an important pathogenesis of hypertensive renal injury. We previously reported the protective effect VEGFR3 in salt-sensitive hypertension. However, specific mechanism underlying role kidney during overactivation renin-angiotensin-aldosterone system remains unclear. In present study, nephropathy was established by angiotensin II (Ang II). found that highly increased PTCs Ang II-infused mice. Activation mitigated dysfunction, pathological damage, and oxidative stress II-induced Moreover, we restored mitophagy deficiency induced both vivo vitro to alleviate injury PTCs. Furthermore, experiment demonstrated improved abnormal enhancing PARKIN mitochondrial translocation. LC-MS/MS Co-IP assays identified HSPA1L as interacted protein VEGFR3, which promoted translocation PARKIN. Mechanistically, disorder domain bound HSPA1L, crotonylation modification at K130 required for regulation context Finally, on were attenuated transfection (HSPA1L-K130R) mutant plasmid vitro. These findings indicated alleviated promoting PARKIN-dependent pathway via regulating site PTCs, provided a mechanistic basis therapeutic target

Language: Английский

Citations

2
Lymphatic endothelial-like cells promote glioblastoma stem cell growth through cytokine-driven cholesterol metabolism DOI
Linjie Zhao, Zhixin Qiu, Zhengnan Yang

et al.

Nature Cancer, Journal Year: 2024, Volume and Issue: 5(1), P. 147 - 166

Published: Jan. 3, 2024

Language: Английский

Citations

15