Cellular signalling最新文献

{"title":"Glycolytic reprogramming in microglia: A potential therapeutic target for ischemic stroke","authors":"","doi":"10.1016/j.cellsig.2024.111466","DOIUrl":"10.1016/j.cellsig.2024.111466","url":null,"abstract":"<div><div>Ischemic stroke is currently the second leading cause of mortality worldwide, with limited treatment options available. As resident immune cells, microglia promptly respond to cerebral ischemic injury, influencing neuroinflammatory damage and neurorepair. Studies suggest that microglia undergo metabolic reprogramming from mitochondrial oxidative phosphorylation to glycolysis in response to ischemia, significantly impacting their function during ischemic stroke. Therefore, this study aims to investigate the roles and regulatory mechanisms involved in this process, aiming to identify a new therapeutic target or potential drug candidate.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459260","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":"ARL8B promotes hepatocellular carcinoma progression and inhibits antitumor activity of lenvatinib via MAPK/ERK signaling by interacting with RAB2A","authors":"","doi":"10.1016/j.cellsig.2024.111470","DOIUrl":"10.1016/j.cellsig.2024.111470","url":null,"abstract":"<div><div>Tumor recurrence and metastasis are important factors affecting postoperative survival in hepatocellular carcinoma (HCC) patients. ADP Ribosylation factor-like GTPase 8B (ARL8B) plays a crucial role in many biological processes, including lysosomal function, immune response, and cellular communication, all of which are related to the occurrence and development of tumors. However, its role in HCC remains unclear. Herein, we revealed that ARL8B is consistently elevated in HCC tissues compared to normal liver tissues, suggesting an unfavorable outcome in HCC patients. Increased ARL8B levels promoted the malignant phenotype of HCC <em>in vitro</em> and <em>in vivo</em>. Notably, ARL8B also induced epithelial-to-mesenchymal transition (EMT) in HCC cells. Mechanistically, the results of bioinformatics analysis combined with mass spectrometry revealed the potential downstream target molecule RAB2A of ARL8B. ARL8B directly interacted with RAB2A and increased the levels of GTP-bound RAB2A, thereby contributing to the activation of the extracellular signal-regulated kinase (ERK) signaling pathway. Interestingly, knockout of ARL8B in Hep3B cells enhanced the antitumor activity of lenvatinib <em>in vitro</em> and <em>in vivo</em>. Furthermore, AAV-shARL8B enhanced the inhibition of HCC growth through lenvatinib, providing new insights into its mechanism of action in lenvatinib-insensitive patients. In conclusion, ARL8B promotes the malignant phenotype of HCC and EMT <em>via</em> RAB2A mediated activation of the MAPK/ERK signaling pathway and is expected to be a valuable prognostic indicator and therapeutic target for HCC patients.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459258","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":"Retraction notice to “Tumor-secreted GRP78 facilitates the migration of macrophages into tumors by promoting cytoskeleton remodeling” [Cellular Signalling volume (60) August 2019, 1–16]","authors":"","doi":"10.1016/j.cellsig.2024.111460","DOIUrl":"10.1016/j.cellsig.2024.111460","url":null,"abstract":"","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459263","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":"Histone methyltransferase WHSC1 cooperate with YBX1 promote glioblastoma progression via regulating PLK1 expression","authors":"","doi":"10.1016/j.cellsig.2024.111471","DOIUrl":"10.1016/j.cellsig.2024.111471","url":null,"abstract":"<div><div>Wolf-Hirschhorn syndrome candidate gene 1 (WHSC1), a histone methyltransferase, has been implicated in various tumor development processes by regulating target gene expression. However, the role of WHSC1 in glioblastoma remains unexplored. This study investigates the impact of WHSC1 in glioblastoma and its association with prognosis. Our findings reveal that WHSC1 is overexpressed in glioblastoma and correlates with poor patient outcomes. Functional assays demonstrate that the reduction of WHSC1 significantly impairs cell proliferation and tumorigenicity. Mechanistically, WHSC1 modulates PLK1 expression by binding to its promoter region, leading to the activation of the PLK1-AKT pathway, and regulating H3K36 dimethylation levels. Furthermore, YBX1 can cooperate with WHSC1 to activate PLK1 transcription. These results shed light on the potential significance of WHSC1 in glioblastoma and offer a promising avenue for future therapeutic approaches targeting this molecule in glioblastoma treatment.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459269","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":"Txnip promotes autophagic apoptosis in diabetic cardiomyopathy by upregulating FoxO1 and its acetylation","authors":"","doi":"10.1016/j.cellsig.2024.111469","DOIUrl":"10.1016/j.cellsig.2024.111469","url":null,"abstract":"<div><div>Autophagy dysfunction and apoptosis exacerbate the risk of heart failure in patients with diabetic cardiomyopathy (DCM). However, the interactions between autophagy and apoptosis in DCM and their underlying mechanisms remain poorly understood. This study induced type 1 DCM in C57BL/6 mice via streptozotocin injection and exposed H9C2 cells to high glucose to investigate these mechanisms. The study revealed a significant elevation in autophagic vesicles and compromised autophagic flux, accompanied by pronounced myocardial cell apoptosis in the myocardium of diabetic mice. Long-term exposure to high glucose in H9C2 cells led to enhanced autophagosome formation and impaired autophagic flux, while inhibition of autophagy with 3-MA reduced cell apoptosis. Additionally, we observed an increase in Txnip expression in the myocardium of diabetic mice and in high glucose-treated H9C2 cells, which regulates autophagic apoptosis in high glucose-treated H9C2 cells. Furthermore, Txnip regulates autophagic apoptosis through the modulation of forkhead box-1 (FoxO1) expression and acetylation. Prolonged high glucose exposure resulted in increased levels of phosphorylated sirtuin 1 (SIRT1) and reduced SIRT1/FoxO1 interaction, changes that were ameliorated by Txnip knockdown. Txnip overexpression elevated FoxO1 levels, which could be suppressed by NAC and GSH. These findings revealed that Txnip mediates autophagic apoptosis in DCM by upregulating FoxO1 via ROS and enhancing FoxO1 acetylation through the suppression of SIRT1 activity. The discovery of this new mechanism provides new perspectives and potential therapeutic targets for understanding and treating DCM.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442886","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":"PRKAA2-mediated mitophagy regulates oxygen consumption in yak renal tubular epithelial cells under chronic hypoxia","authors":"","doi":"10.1016/j.cellsig.2024.111450","DOIUrl":"10.1016/j.cellsig.2024.111450","url":null,"abstract":"<div><div>Hypoxic environments are significant factors in the induction of various kidney diseases and are closely associated with high oxygen consumption in the kidneys. Yaks live at high altitude for a long time, exhibit a unique ability to regulate kidney oxygen consumption, protecting them from hypoxia-induced damage. However, the mechanisms underlying the regulation of oxygen consumption in yak kidneys under hypoxic conditions remain unclear. To explore this hypoxia adaptation mechanism in yak kidneys, this study analyzed the oxygen consumption rate (OCR) of renal tubular epithelial cells (RTECs) under hypoxia. We found that the OCR and apoptosis rates of RTECs under chronic hypoxia (&gt; 24 h) were lower than those under acute hypoxia (≤ 24 h). However, when oxygen consumption was promoted under chronic hypoxia, the apoptosis rate increased, indicating that reducing the cellular OCR is crucial for maintaining RTECs activity under hypoxia. High-throughput sequencing results showed that the mitophagy pathway is likely a key mechanism for inhibiting OCR of yak RTECs, with protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2) playing a significant role in this process. Further studies demonstrated that chronic hypoxia activates the mitophagy pathway, which inhibits oxidative phosphorylation (OXPHOS) while increasing glycolytic flux in yak RTECs. Conversely, when the mitophagy pathway was inhibited, there was an increase in the activity of OXPHOS enzymes and OCR. To further explore the role of PRKAA2 in the mitophagy pathway, we inhibited PRKAA2 expression under chronic hypoxia. Results showed that the downregulation of PRKAA2 decreased the expression of mitophagy-related proteins, such as p-FUNDC1/FUNDC1, LC3-II/LC3-I, BNIP3 and ULK1 while upregulating P62 expression. Additionally, there was an increase in the enzyme activities of Complex II, Complex IV, PDH, and SDH, which further promoted oxygen consumption in RTECs. These findings suggest that PRKAA2 mediated mitophagy under chronic hypoxia is crucial mechanism for reducing oxygen consumption in yak RTECs.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445316","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":"Enriched environment enhances angiogenesis in ischemic stroke through SDF-1/CXCR4/AKT/mTOR pathway","authors":"","doi":"10.1016/j.cellsig.2024.111464","DOIUrl":"10.1016/j.cellsig.2024.111464","url":null,"abstract":"<div><div>Environmental-gene interactions significantly influence various bodily functions. Enriched environment (EE), a non-pharmacological treatment method, enhances angiogenesis in ischemic stroke (IS). However, underlying the role of EE in angiogenesis in aged mice post-IS remain unclear. This study aimed to determine the potential mechanism by which EE mediates angiogenesis in 12-month-old IS mice and oxygen-glucose deprivation/reperfusion (OGD/R)-induced bEnd.3 cells. <em>In vivo</em>, EE treatment alleviated the neurological deficits, enhanced angiogenesis, upregulated SDF-1, VEGFA, and the AKT/mTOR pathway. In addition, exogenous SDF-1 treatment had a protective effect similar to that of EE treatment in aged mice with IS. However, SDF-1 neutralizing antibody, AMD3100 (CXCR4 inhibitor), ARQ092 (AKT inhibitor), and rapamycin (mTOR inhibitor) treatment blocked the neuroprotective effect of EE treatment and inhibited angiogenesis in IS mice. <em>In vitro</em>, exogenous SDF-1 promoted migration of OGD/R-induced bEnd.3 cells and activated the AKT/mTOR pathway. AMD3100, ARQ092, and rapamycin inhibited SDF-1-induced cell migration. Collectively, these findings demonstrate that EE enhances angiogenesis and improves the IS outcomes through SDF-1/CXCR4/AKT/mTOR pathway.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459266","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":"Forkhead box C1 promotes the pathology of osteoarthritis in subchondral bone osteoblasts via the Piezo1/YAP axis","authors":"","doi":"10.1016/j.cellsig.2024.111463","DOIUrl":"10.1016/j.cellsig.2024.111463","url":null,"abstract":"<div><div>Subchondral bone sclerosis is a key characteristic of osteoarthritis (OA). Prior research has shown that Forkhead box C1 (FoxC1) plays a role in the synovial inflammation of OA, but its specific role in the subchondral bone of OA has not been explored. Our research revealed elevated expression levels of FoxC1 and Piezo1 in OA subchondral bone tissues. Further experiments on OA subchondral bone osteoblasts with FoxC1 or Piezo1 overexpression showed increased cell proliferation activity, expression of Yes-associated Protein 1 (YAP) and osteogenic markers, and secretion of proinflammatory factors. Mechanistically, the overexpression of FoxC1 through Piezo1 activation, in combination with downstream YAP signaling, led to increased levels of alkaline phosphatase (ALP), collagen type 1 (COL1) A1, RUNX2, Osteocalcin, matrix metalloproteinase (MMP) 3, and MMP9 expression. Notably, inhibition of Piezo1 reversed the regulatory function of FoxC1. The binding of FoxC1 to the targeted area (ATATTTATTTA, residues +612 to +622) and the activation of Piezo1 transcription were verified by the dual luciferase assays. Additionally, Reduced subchondral osteosclerosis and microangiogenesis were observed in knee joints from FoxC1-conditional knockout (CKO) and Piezo1-CKO mice, indicating reduced lesions. Collectively, our study reveals the significant involvement of FoxC1 in the pathologic process of OA subchondral bone via the Piezo1/YAP signaling pathway, potentially establishing a novel therapeutic target.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445317","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":"Histone H4K12 lactylation promotes malignancy progression in triple-negative breast cancer through SLFN5 downregulation","authors":"","doi":"10.1016/j.cellsig.2024.111468","DOIUrl":"10.1016/j.cellsig.2024.111468","url":null,"abstract":"<div><div>Lactylation, a newly identified post-translational modification, is uncertain in its implication in triple-negative breast cancer (TNBC). In this study, we analyzed 60 TNBC samples using immunohistochemical staining and revealed elevated levels of pan-lactylated proteins and specific histone H4K12 lactylation in tumor tissues, correlating with TNBC progression. Lactate exposure in TNBC cell lines significantly induced lysine lactylation at the H4K12 site, leading to alterations in gene profiles and reduced apoptosis. These effects were attenuated by DCA or sodium Oxamate, inhibitors of endogenous lactate production. Gene sequencing showed an increase in Schlafen 5 (SLFN5) expression in TNBC cells treated with Oxamate, contrasting with the effects of lactate exposure. Analysis of TNBC tissues showed a negative correlation between H4K12 lactylation and SLFN5 protein levels. Overexpression of SLFN5 countered the effects of lactate on apoptosis and tumor growth, highlighting its pivotal role in TNBC malignancy. CUT&amp;Tag sequencing indicated that lactylated H4K12 potentially binds to the SLFN5 promoter region. Luciferase reporter assays further verified that lactate-induced suppression of SLFN5 promoter activity is mediated by wild-type H4K12, but not by its R or A mutants, verified by both in vitro and in vivo apoptosis detection in response to lactate and Oxamate stimulation. These results establish that H4K12 lactylation, induced by lactate in TNBC cells, specifically suppresses SLFN5 expression, contributing to TNBC malignancy. Our findings illuminate a critical histone lactylation-dependent carcinogenic pathway in TNBC.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459268","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 “Recent progress of protein kinase inhibitors derived from marine peptides for developing anticancer gents” [Cellular Signalling 124 (2024) 111411]","authors":"","doi":"10.1016/j.cellsig.2024.111449","DOIUrl":"10.1016/j.cellsig.2024.111449","url":null,"abstract":"","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399549","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}