Cellular signalling最新文献

{"title":"Mechanism underlying CDC20 affecting epithelial ovarian cancer biological behavior by regulating BAG6 ubiquitination","authors":"Xiaocui Zhang,&nbsp;Fangfang Bi,&nbsp;Qing Yang","doi":"10.1016/j.cellsig.2024.111577","DOIUrl":"10.1016/j.cellsig.2024.111577","url":null,"abstract":"<div><div>Epithelial ovarian cancer (EOC) endangers women's life and health. It is reported that cell division cycle 20 (CDC20) plays a role in EOC, but its underlying mechanisms remain unclear. Additionally, the involvement of bcl-2-associated athanogen-6 (BAG6) in EOC has not been previously reported. This study demonstrated that CDC20 was highly expressed in EOC and exhibited oncogenic properties through both in vitro and in vivo molecular biology experiments. In contrast, BAG6 was low expressed and functioned as a tumor suppressor. Both CDC20 and BAG6 were found to correlate with patient stage. Notably, the degradation of BAG6, mediated by CDC20 via ubiquitin-proteasome pathway, was shown to enhance the malignant biological behavior of EOC. Furthermore, the interaction between CDC20 and BAG6 was dependent on the WD40 domain of CDC20 and the D-box of BAG6. These findings provided valuable insights into the molecular mechanisms of EOC and established a theoretical basis for novel therapeutic targets in clinical treatment.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111577"},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALKBH5 promotes cardiac fibroblasts pyroptosis after myocardial infarction through Notch1/NLRP3 pathway","authors":"Liu-Gen Cui ,&nbsp;Shu-Hui Wang ,&nbsp;Sumra Komal ,&nbsp;Jian-Jian Yin ,&nbsp;Miao-Miao Zhai ,&nbsp;Yue-Jiao Zhou ,&nbsp;Qing-Wen Yu ,&nbsp;Cong Wang ,&nbsp;Pei Wang ,&nbsp;Zhi-Mo Wang ,&nbsp;Aliza Muhammad Zafar ,&nbsp;Muhammad Shakeel ,&nbsp;Li-Rong Zhang ,&nbsp;Sheng-Na Han","doi":"10.1016/j.cellsig.2024.111574","DOIUrl":"10.1016/j.cellsig.2024.111574","url":null,"abstract":"<div><div>Through bioinformatics screening, we previously found that AlkB homolog 5 (ALKBH5) expression, an m⁶A demethylase, was higher in patients with heart failure than in the normal population. This study aimed to investigate the molecular mechanisms by which ALKBH5 regulates heart failure. We established a myocardial infarction (MI)-induced heart failure model in rats in vivo and an in vitro hypoxia model using rat primary cardiac fibroblasts (RCFs). M⁶A sequencing, RNA immunoprecipitation assay, RNA pull-down assay, proximity ligation assay, gain-of-function and loss-of-function experiments, and transcriptomic analysis were performed to confirm the pyroptosis-promoting effects of ALKBH5. The effects of two small-molecule inhibitors (ZINC78774792 and ZINC00546946) on ALKBH5 expression were examined. The expression of m⁶A demethyltransferase ALKBH5 was significantly elevated in hypoxia-induced RCFs. Transcriptional profiling revealed Notch receptor 1 (Notch1) as an m⁶A modification target of ALKBH5, and Notch1 mRNA m⁶A modifications were increased in ALKBH5-deficient RCFs. Moreover, Notch1 and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) are associated. ALKBH5 knockdown alleviated hypoxia-induced RCF cell pyroptosis by inhibiting Notch1, NLRP3 inflammasome activation, and pyroptosis-associated protein (N-GSDMD), whereas ALKBH5 overexpression had the opposite effect. Targeting ALKBH5 with two small-molecule inhibitors (ZINC78774792 and ZINC00546946) reduced hypoxia-induced RCF pyroptosis, and ZINC00546946 alleviated cell pyroptosis after myocardial infarction in mice. Our results indicate that ALKBH5 promotes cardiac fibroblast pyroptosis after myocardial infarction through the Notch1/NLRP3 pathway. Therefore, inhibiting ALKBH5 may be a strategy for treating cardiovascular diseases.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111574"},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3-mediated m6A modifications of NLRP3 accelerate alveolar bone resorption through enhancing macrophage pyroptosis","authors":"Qiudong Yang ,&nbsp;Junhong Xiao ,&nbsp;Yuqi Liu ,&nbsp;Zhengkun Yang ,&nbsp;Chuan Wang ,&nbsp;Jiahui Sun ,&nbsp;Huiyi Wang ,&nbsp;Heyu Liu ,&nbsp;Xiaoxuan Wang ,&nbsp;Li Ma ,&nbsp;Xin Huang ,&nbsp;Zhengguo Cao","doi":"10.1016/j.cellsig.2024.111572","DOIUrl":"10.1016/j.cellsig.2024.111572","url":null,"abstract":"<div><div>Periodontitis (PD) is twice as prevalent in diabetics compared to nondiabetics, and diabetes-associated PD is characterized by increased inflammation and aggravated tissue damage. Pyroptosis has recently been implicated in diabetes-associated PD; however, the underlying mechanisms remain largely unknown, resulting in a lack of effective treatments. In this study, we investigated the role of methyltransferase-like 3 (METTL3) in macrophage pyroptosis and found that it inhibits the osteogenic differentiation of osteoblasts via pyroptotic macrophages in a diabetes-associated periodontitis mouse model. Further analysis and validation revealed that nod-like receptor family pyrin domain-containing 3 (NLRP3) is a target of METTL3, with its mRNA stability regulated through a binding of insulin-like growth factor 2 binding protein 3 (IGF2BP3)-dependent pathway. Additionally, local injection of adeno-associated virus 9 (AAV9) demonstrated that METTL3 deficiency in macrophages significantly ameliorates periodontal inflammation and alveolar bone loss in diabetes-associated PD mice. Collectively, our findings indicate that METTL3-mediated modulation of NLRP3 expression is a crucial factor in macrophage pyroptosis during diabetes-associated PD progression. This suggests that the METTL3/IGF2BP3/NLRP3 axis is a novel and promising target for the improvement of periodental inflammation and alveolar bone loss in diabetes-associated PD.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111572"},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of AXL as a novel positive regulator of lipid raft in gastric cancer","authors":"Zhi Yang ,&nbsp;Chuanfu Ren ,&nbsp;Ziyun He ,&nbsp;Banxin Luo ,&nbsp;Xin Chen ,&nbsp;En Xu ,&nbsp;Wenxian Guan ,&nbsp;Xuefeng Xia","doi":"10.1016/j.cellsig.2024.111573","DOIUrl":"10.1016/j.cellsig.2024.111573","url":null,"abstract":"<div><div>Lipid rafts are highly heterogeneous and dynamic microdomains involved in molecule trafficking and signaling transduction. This study investigates the role of lipid rafts in gastric cancer and their key regulators. Analyzing FFPE samples from 111 gastric cancer patients, we found that high lipid raft levels predict poor prognosis. Modulating these levels in gastric cancer cell lines significantly impacted cell proliferation, migration, and invasion. Weighted Gene Co-expression Network Analysis identified AXL as a hub gene associated with lipid rafts. AXL knockdown experiments revealed its interaction with Caveolin-1, a caveolae lipid raft protein, which regulates lipid raft levels and promotes AKT and ERK signaling, enhancing cancer development and metastasis. In vivo tumorigenesis assays and survival analyses further supported these findings. This study underscores the significance of lipid rafts in gastric cancer and identifies AXL as a novel regulator, offering new insights into the molecular mechanisms of cancer progression and suggesting potential therapeutic targets.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111573"},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Iron depletion suppresses mTORC1-directed signalling in intestinal Caco-2 cells via induction of REDD1” [Cellular Signalling, 28: (2016) 412–424]","authors":"Ailsa Watson ,&nbsp;Christopher Lipina ,&nbsp;Harry J. McArdle ,&nbsp;Peter M. Taylor ,&nbsp;Harinder S. Hundal","doi":"10.1016/j.cellsig.2024.111567","DOIUrl":"10.1016/j.cellsig.2024.111567","url":null,"abstract":"","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111567"},"PeriodicalIF":4.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet inhibition by hypochlorous acid involves cAMP signalling","authors":"Lorna O'Donoghue ,&nbsp;Dishon Hiebner ,&nbsp;Roopesh Krishnankutty ,&nbsp;Ingmar Schoen ,&nbsp;Alex von Kriegsheim ,&nbsp;Albert Smolenski","doi":"10.1016/j.cellsig.2024.111568","DOIUrl":"10.1016/j.cellsig.2024.111568","url":null,"abstract":"<div><div>Hypochlorous acid (HOCl), made by neutrophil-derived myeloperoxidase, has been suggested to inhibit platelets, however, the mechanisms involved have not been described. Here we confirm that HOCl exposure changes platelet morphology and inhibits platelet spreading and aggregation. HOCl effects could be reversed by glutathione suggesting a role for cysteine oxidation. Mass spectrometry-based proteomics of HOCl-exposed platelets revealed oxidised cysteine residues in 37 proteins including adenylate cyclase 6 and Rap1B. Adenylate cyclase is involved in the inhibitory cAMP pathway triggered by endothelium-derived prostacyclin and Rap1 is a small G protein required for integrin αIIbβ3 activation and platelet aggregation. We show that HOCl exposure stimulates cAMP production and phosphorylation of the cAMP-dependent protein kinase substrate VASP in platelets and transfected HEK293T cells. In addition, HOCl inhibited Rap1-GTP formation. These data suggest that HOCl inhibits platelets at least in part through the cAMP pathway and by regulating Rap1. Thus, this study provides new insights into HOCl mediated crosstalk between neutrophils and platelets.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111568"},"PeriodicalIF":4.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disulfiram/Cu targeting FOXO6 modulates sensitivity of hepatocellular carcinoma to lenvatinib via disrupt choline metabolic","authors":"Shiyi Wu ,&nbsp;Jialu Weng ,&nbsp;Yating Pan ,&nbsp;Zhikai Wen ,&nbsp;Jing Zeng ,&nbsp;Yunwei Lou ,&nbsp;Songjian Tong ,&nbsp;Pan Liao ,&nbsp;Na Li ,&nbsp;Zhijie Yu ,&nbsp;Jinglin Xia","doi":"10.1016/j.cellsig.2024.111563","DOIUrl":"10.1016/j.cellsig.2024.111563","url":null,"abstract":"<div><div>Disulfiram/Cu(DSF/Cu) has a known pharmacokinetic and safety profile, exerting a strong antitumor effect. Oral tyrosine kinase inhibitors including lenvatinib are approved as first-line therapy for treating advanced unresectable hepatocellular carcinoma (HCC). These patients still have limited survival due to drug resistance. Disulfiram/Cu and lenvatinib are the promising antitumor treatments. In this study, we studied whether Disulfiram/Cu increased lenvatinib sensitivity in HCC cells. Moreover, the potential drug targets of Disulfiram/Cu and associated mechanisms were explored. We mainly investigated Autophagic flux was determined via immunofluorescence analysis and confocal microscopy. p-PI3K, p-AKT, p62, LC3B, FOXO6, and CHKA proteins associated with autophagy were detected by immunoblotting. In addition, antitumour activity of Disulfiram/Cu in combination with lenvatinib was examined in vivo through construction of the nude mouse transplant tumor model. Furthermore, our results show disulfiram/Cu combined with lenvatinib exerted the synergistic impact on treating HCC in vitro. Mechanistically, transcriptome combined with metabolome reveals Disulfiram/Cu targeting FOXO6 induction of autophagy mediated inhibits cell growth in hepatocellular carcinoma by downregulating CHKα for inhibiting AKT pathway activation while blocking choline metabolic reprogramming in HCC. These effects mostly explain the tumor-promoting effect of FOXO6 on HCC. In general, the results illustrate the mechanistic associations between metabolites and tumor cell malignant phenotype, contributing to developing new anti-HCC pharmacological treatments by Inhibiting FOXO6 for disrupting choline metabolic pathway.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111563"},"PeriodicalIF":4.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT5-mediated GLS and GDH desuccinylation attenuates the autophagy of bovine mammary epithelial cells induced by ammonia","authors":"Hanlin Yang ,&nbsp;Shikai Gao ,&nbsp;Guangyang Lu ,&nbsp;Junhui He ,&nbsp;Jinru Dong ,&nbsp;Xinyi Zhang ,&nbsp;Luya Liu ,&nbsp;Kai Zhong ,&nbsp;Guangming Zha ,&nbsp;Liqiang Han ,&nbsp;Shuang Guo ,&nbsp;Heping Li ,&nbsp;Yueying Wang","doi":"10.1016/j.cellsig.2024.111570","DOIUrl":"10.1016/j.cellsig.2024.111570","url":null,"abstract":"<div><div>Sirtuin 5 (SIRT5) in mitochondria possesses a strong capacity for lysine desuccinylation, involving in various biological processes. Our previous research demonstrated that NH₃ regulated autophagy dependent on SIRT5 in bovine mammary epithelial cells (bMECs). Interestingly, we discovered that SIRT5 reduced the content of NH₃ and glutamate by inhibiting GLS activity in bMECs, the ratio of ADP/ATP also declined. In this study, we identified that SIRT5 interacted with endogenous GLS and GDH through Co-IP assay, but had no effect on endogenous GLS and GDH expression. SIRT5 made the succinylation levels of GLS and GDH significantly declined and resulted in the reduction of GLS and GDH activity. Next, the content of ammonia and glutamate, as well as the related autophagy markers were measured, we found that SIRT5 affected the glutamine metabolism, which attenuated ammonia release in MAC-T cells, accompanying with cellular autophagy decline, reducing the formation of autophagosome. Deletion of SIRT5 gene in MAC-T cells by means of CRISPR-cas9, we found the content of NH₃ and glutamate increased, as well as autophagy promoted, which could be alleviated by SIRT5 overexpression. SIRT5 KO also resulted in increase of succinylation of GLS and GDH, as well as autophagy response in bMECs. Furthermore, SIRT5 promoted the maintenance of mitochondria homeostasis. Mechanistically, SIRT5 reduced ammonia release by modulating the succinylation levels and enzymatic activities of GLS and GDH in mitochondria and promoted the maintenance of mitochondria homeostasis, as well as further attenuated ammonia-stimulated autophagy in bovine mammary epithelial cells.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111570"},"PeriodicalIF":4.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overexpression of Nogo-A changes nerve growth factor signaling dynamics in PC12 cells","authors":"Robert G. Farrer ,&nbsp;Gwendolyn L. Kartje","doi":"10.1016/j.cellsig.2024.111569","DOIUrl":"10.1016/j.cellsig.2024.111569","url":null,"abstract":"<div><div>The nerve growth factor (NGF) receptor TrkA is a tightly regulated receptor tyrosine kinase that activates neuronal signaling pathways promoting cell survival in addition to axonal and dendritic outgrowth. Previously, we showed that NGF and TrkA signaling is altered in neuron-like PC12 cells that overexpress Nogo-A, a protein known to influence axonal outgrowth and dendritic arborization associated with neuronal plasticity. In the present report, we provide evidence for changes in NGF-mediated receptor-level and downstream signaling that occur in cells overexpressing Nogo-A. NGF stimulation increased the association of Nogo-A with TrkA, which corresponded to a decrease in sustained phosphorylation of TrkA and its downstream effectors Erk1/2, indicating that Nogo-A plays a role in the temporal regulation of this pathway. Furthermore, co-immunoprecipitation of the p75 neurotrophin receptor (p75^NTR) with TrkA was significantly reduced in cells overexpressing Nogo-A, suggesting that Nogo-A blocked this interaction. Analysis of calcium and calmodulin involvement in NGF-induced activation of Erk1/2 revealed a calcium and calmodulin-dependent inhibition of sustained phosphorylation in Nogo-A-overexpressing cells but not in wild type cells, suggesting that Nogo-A facilitated the activation of calcium/calmodulin to alter NGF signaling. Taken together, these results provide evidence for Nogo-A regulation of NGF signaling, in part by modifying calcium and calmodulin-dependent mechanisms.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111569"},"PeriodicalIF":4.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kynureninase induce cuproptosis resistance in gastric cancer progression through downregulating lipotic acid synthetase mediated non-canonical mechanism","authors":"Yuanda Liu ,&nbsp;Changfeng Li ,&nbsp;Xilun Cui ,&nbsp;Chang Liu ,&nbsp;Pengtuo Xiao ,&nbsp;Wei Yang","doi":"10.1016/j.cellsig.2024.111565","DOIUrl":"10.1016/j.cellsig.2024.111565","url":null,"abstract":"<div><h3>Background</h3><div>Gastric cancer (GC) is among the most malignant tumors, with the lowest five-year survival rate, and limited treatment options. Kynureninase (KYNU), is a key molecule in tryptophan metabolism and promotes tumor progression and immunosuppression. Cuproptosis is a non-apoptotic cell death mechanism, primarily due to oxidative stress caused by copper ion accumulation, that is related to tumor progression and drug resistance. KYNU can inhibit ferroptosis of tumor cells by alleviating oxidative stress. Here, we explored whether KYNU can regulate the biological behavior of GC and cuproptosis.</div></div><div><h3>Methods</h3><div>Expression, prognostic association, and functional analysis of KYNU in GC and tumor-adjacent tissues were analyzed using data from The Cancer Genome Atlas and clinical specimens. Effects of KYNU on proliferation, invasion, metastasis, and cuproptosis of GC cells were detected by CCK8, clone formation, Transwell, and flow cytometry assays. Elesclomol (ES) combined with CuCl₂ were used to induce cuproptosis in GC cells. 3-hydroxyanthranilic acid (3-HA) was used to indicate KYNU function. Key cuproptosis genes were detected by qPCR and WB. The effects of KYNU on GC cell behavior and cuproptosis through lipoic acid synthetase (LIAS) were verified by stable overexpression and knockdown of LIAS.</div></div><div><h3>Results</h3><div>KYNU is highly expressed in GC, and high KYNU expression is an independent predictor of poor prognosis in patients with GC. KYNU can promote GC cell proliferation, invasion, metastasis, and cuproptosis resistance. 3-HA had a certain inhibitory effect on the expression of LIAS, but it was not significant. KYNU had no effect on the intracellular 3-HA level. KYNU expression was negatively correlated with that of LIAS, and promoted GC cell proliferation, invasion, metastasis, and cuproptosis resistance by downregulating LIAS.</div></div><div><h3>Conclusions</h3><div>KYNU can promote GC proliferation, invasion, metastasis, and cuproptosis resistance.This effect is not associated with its metabolite 3-HA, but is achieved by a non classical mechanisms that downregulating the expression of LIAS, a key gene of cuproptosis.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111565"},"PeriodicalIF":4.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}