Cellular signalling最新文献_第9页

Integrative analysis of FADS3 as a marker for prognosis and immunity in head and neck squamous cell carcinoma 将 FADS3 作为头颈部鳞状细胞癌预后和免疫标志物的综合分析。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-09-27 DOI: 10.1016/j.cellsig.2024.111437

Haonan Tang , Yanlin Geng , Keyi Wang , Yuchi Zhu , Yuan Fan , Yanting Wang

{"title":"Integrative analysis of FADS3 as a marker for prognosis and immunity in head and neck squamous cell carcinoma","authors":"Haonan Tang , Yanlin Geng , Keyi Wang , Yuchi Zhu , Yuan Fan , Yanting Wang","doi":"10.1016/j.cellsig.2024.111437","DOIUrl":"10.1016/j.cellsig.2024.111437","url":null,"abstract":"<div><h3>Background</h3><div>Long-chain polyunsaturated fatty acid formation requires fatty acid desaturase (FADS), which is strongly linked to cancer progression. Nevertheless, it's unclear how FADS3 functions in head and neck squamous cell carcinoma (HNSCC).</div></div><div><h3>Methods</h3><div>HNSCC cases were retrieved from TCGA and GEO databases, and FADS members with transcriptionally differential expression were identified. Clinical survival, tumor microenvironment (TME), and potential pathogenic mechanism in HNSCC were also investigated. These results were validated using tissue staining, flow cytometry and functional studies in HNSCC cell lines.</div></div><div><h3>Results</h3><div>When comparing HNSCC to normal epithelial tissues, FADS3 expression was much higher in the former. FADS3 upregulation was correlated with poor clinical outcomes. FADS3 was an independent prognostic factor for poor overall survival in HNSCC patients. KEGG, GO, and GSEA revealed that FADS3 expression correlated with several immune-related pathways and the epithelial-mesenchymal transition (EMT). Knocking down FADS3 restrained HNSCC cell proliferation, migration, invasion, and EMT. Single-cell dataset analysis showed an association between FADS3 and TME features. Further investigation revealed that FADS3<sup>high</sup> tumor was accompanied with less CD8<sup>+</sup> T cells in situ tissue and peripheral blood. FADS3 was positively correlated with immune-related molecules and could predict the adverse efficacy of immunotherapy. Finally, we constructed a CYTOR/hsa-let-7c-5p axis regulating FADS3 expression in HNSCC progression.</div></div><div><h3>Conclusions</h3><div>FADS3 may represent a target for treatment in HNSCC, which is linked to prognosis, EMT, immune infiltration, and ceRNA regulatory network of HNSCC.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111437"},"PeriodicalIF":4.4,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342642","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}

引用次数: 0

Transcriptional upregulation of MMP-9 gene under hyperglycemic conditions in AGS cells: Role of AP-1 transcription factor 高血糖条件下 AGS 细胞中 MMP-9 基因的转录上调：AP-1 转录因子的作用

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-09-25 DOI: 10.1016/j.cellsig.2024.111435

Abhishek Chatterjee, Tapasi Roy, Snehasikta Swarnakar

{"title":"Transcriptional upregulation of MMP-9 gene under hyperglycemic conditions in AGS cells: Role of AP-1 transcription factor","authors":"Abhishek Chatterjee, Tapasi Roy, Snehasikta Swarnakar","doi":"10.1016/j.cellsig.2024.111435","DOIUrl":"10.1016/j.cellsig.2024.111435","url":null,"abstract":"<div><div>Gastric cancer and diabetes are two complex and interrelated diseases having significant impact on global health. Hyperglycemic condition notably exacerbates cancer by promoting inflammation, angiogenesis, and metastasis. Elevated glucose levels can also upregulate the expression of specific matrix metalloproteinases (MMPs), especially MMP-9, which is associated with cancer cell migration and invasion. However, the molecular mechanism behind such upregulation remains unexplored. In the present study, we have identified the mechanism for hyperglycemia-induced transcriptional activation of MMP-9, in gastric adenocarcinoma (AGS) cells. Using various tools like luciferase-reporter assays with promoter deletion constructs, siRNAs, pharmacological inhibitors, and nuclear translocation experiments, we have identified that the transcriptional activation of MMP-9 under hyperglycemic conditions is predominantly governed by the MAPK pathway, via formation of the AP-1 heterodimer. The p65 NF-κB signaling pathway, although activated, plays no significant role in regulating hyperglycemia-induced MMP-9 expression. Chromatin immunoprecipitation studies indicate that the distal AP-1 binding site is responsible for hyperglycemia-induced MMP-9 transcription; whereas the proximal one accounts for both hyperglycemia-induced and basal MMP-9 transcription. Therefore, binding of AP-1 at both the proximal and distal binding sites on the MMP-9 promoter region is required for hyperglycemia-induced MMP-9 expression. Overall, our study unveils a novel mechanism of MMP-9 transcription under hyperglycemic conditions and also suggests that inhibiting the binding of the AP-1 heterodimer with its distal binding site can potentially reduce the complications developed during gastric cancer-hyperglycemia co-morbidity. A drug designed specifically to inhibit this interaction may prevent hyperglycemia-induced tumor aggressiveness to a considerable extent by impeding MMP-9 transcription.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111435"},"PeriodicalIF":4.4,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342644","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}

引用次数: 0

A comprehensive review of PRAME and BAP1 in melanoma: Genomic instability and immunotherapy targets 全面回顾黑色素瘤中的 PRAME 和 BAP1：基因组不稳定性和免疫疗法靶点。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-09-24 DOI: 10.1016/j.cellsig.2024.111434

Alaa A.A. Aljabali , Murtaza M. Tambuwala , Mohamed El-Tanani , Sk. Sarif Hassan , Kenneth Lundstrom , Vijay Mishra , Yachana Mishra , Altijana Hromić-Jahjefendić , Elrashdy M. Redwan , Vladimir N. Uversky

{"title":"A comprehensive review of PRAME and BAP1 in melanoma: Genomic instability and immunotherapy targets","authors":"Alaa A.A. Aljabali , Murtaza M. Tambuwala , Mohamed El-Tanani , Sk. Sarif Hassan , Kenneth Lundstrom , Vijay Mishra , Yachana Mishra , Altijana Hromić-Jahjefendić , Elrashdy M. Redwan , Vladimir N. Uversky","doi":"10.1016/j.cellsig.2024.111434","DOIUrl":"10.1016/j.cellsig.2024.111434","url":null,"abstract":"<div><div>In a thorough review of the literature, the complex roles of <em>PRAME</em> (preferentially expressed Antigen of Melanoma) and <em>BAP1</em> (BRCA1-associated protein 1) have been investigated in uveal melanoma (UM) and cutaneous melanoma. High <em>PRAME</em> expression in UM is associated with poor outcomes and correlated with extraocular extension and chromosome 8q alterations. <em>BAP1</em> mutations in the UM indicate genomic instability and a poor prognosis. Combining <em>PRAME</em> and <em>BAP1</em> immunohistochemical staining facilitates effective risk stratification. Mechanistically, both genes are associated with genomic instability, making them promising targets for cancer immunotherapy. Hypomethylation of <em>PRAME</em>, specifically in its promoter regions, is critical for UM progression and contributes to epigenetic reprogramming. Additionally, miR-211 regulation is crucial in melanoma and has therapeutic potential. The way <em>PRAME</em> changes signaling pathways provides clues about the cause of cancer due to genomic instability related to modifications in DNA repair. Inhibition of poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 in cells expressing <em>PRAME</em> could lead to potential therapeutic applications. Pathway enrichment analysis underscores the significance of <em>PRAME</em> and <em>BAP1</em> in melanoma pathogenesis.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111434"},"PeriodicalIF":4.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342639","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}

引用次数: 0

Gelsolin controls the release of phosphatidylserine (PS)-positive microvesicles (MVs) from platelets 凝胶素控制着血小板中磷脂酰丝氨酸（PS）阳性微囊泡（MV）的释放。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-09-24 DOI: 10.1016/j.cellsig.2024.111433

Manoj Paul , Felix Hong , Hervé Falet , Hugh Kim

{"title":"Gelsolin controls the release of phosphatidylserine (PS)-positive microvesicles (MVs) from platelets","authors":"Manoj Paul , Felix Hong , Hervé Falet , Hugh Kim","doi":"10.1016/j.cellsig.2024.111433","DOIUrl":"10.1016/j.cellsig.2024.111433","url":null,"abstract":"<div><div>Upon activation by vascular injury or extracellular agonists, platelets undergo rapid change shape, a process regulated by the actin cytoskeleton and accessory proteins. Platelet shape change is accompanied by the secretion of hemostatic factors and immunomodulatory cytokines from their intracellular granules, as well as the release of microvesicles (MVs) containing pro-inflammatory cytokines and procoagulant phosphatidylserine (PS). However, the role of actin dynamics in MV generation remains unclear. In this study, we found that blocking actin polymerization with cytochalasin D attenuated the release of PS-positive MVs in human platelets stimulated by thrombin or the calcium ionophore A23187. The actin-severing protein gelsolin (Gsn) facilitates normal actin filament turnover in activated platelets. Platelets from Gsn-deficient (<em>Gsn</em><sup><em>−/−</em></sup>) mice showed reduced MV release compared to platelets from control mice. These findings indicate that the proper dynamics of the actin cytoskeleton are essential for MV generation in platelets, which has implications for their pro-inflammatory and procoagulant functions.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111433"},"PeriodicalIF":4.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342643","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}

引用次数: 0

Principle role of the (pro)renin receptor system in cardiovascular and metabolic diseases: An update 前）肾素受体系统在心血管和代谢疾病中的原理作用：最新进展

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-09-23 DOI: 10.1016/j.cellsig.2024.111417

Mengzhi Zhu , Xiaoli Yi , Shanshan Song , Huiru Yang , Jun Yu , Chuanming Xu

{"title":"Principle role of the (pro)renin receptor system in cardiovascular and metabolic diseases: An update","authors":"Mengzhi Zhu , Xiaoli Yi , Shanshan Song , Huiru Yang , Jun Yu , Chuanming Xu","doi":"10.1016/j.cellsig.2024.111417","DOIUrl":"10.1016/j.cellsig.2024.111417","url":null,"abstract":"<div><div>(Pro)renin receptor (PRR), along with its soluble form, sPRR, functions not only as a crucial activator of the local renin-angiotensin system but also engages with and activates various angiotensin II-independent signaling pathways, thus playing complex and significant roles in numerous physiological and pathophysiological processes, including cardiovascular and metabolic disorders. This article reviews current knowledge on the intracellular partners of the PRR system and explores its physiological and pathophysiological impacts on cardiovascular diseases as well as conditions related to glucose and lipid metabolism, such as hypertension, heart disease, liver disease, diabetes, and diabetic complications. Targeting the PRR system could emerge as a promising therapeutic strategy for treating these conditions. Elevated levels of circulating sPRR might indicate the severity of these diseases, potentially serving as a biomarker for diagnosis and prognosis in clinical settings. A comprehensive understanding of the functions and regulatory mechanisms of the PRR system could facilitate the development of novel therapeutic approaches for the prevention and management of cardiovascular and metabolic diseases.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111417"},"PeriodicalIF":4.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314207","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}

引用次数: 0

Noncoding RNA network crosstalk in organ fibrosis 器官纤维化中的非编码 RNA 网络串扰

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-09-21 DOI: 10.1016/j.cellsig.2024.111430

Hui Ling , Xian-Chen Wang , Zhi-Yan Liu , Sui Mao , Jing-Jing Yang , Ji-Ming Sha , Hui Tao

{"title":"Noncoding RNA network crosstalk in organ fibrosis","authors":"Hui Ling , Xian-Chen Wang , Zhi-Yan Liu , Sui Mao , Jing-Jing Yang , Ji-Ming Sha , Hui Tao","doi":"10.1016/j.cellsig.2024.111430","DOIUrl":"10.1016/j.cellsig.2024.111430","url":null,"abstract":"<div><div>Fibrosis is a process involving excessive accumulation of extracellular matrix components, the severity of which interferes with the function of the organ in question. With the advances in RNA sequencing and in-depth molecular studies, a large number of current studies have pointed out the irreplaceable role of non-coding RNAs (ncRNAs) in the pathophysiological development of organ fibrosis. Here, by summarizing the results of a large number of studies on the interactions between ncRNAs, some studies have found that long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), among others, are able to act as sponges or decoy decoys for microRNAs (miRNAs), act as competing endogenous RNAs (ceRNAs) to regulate the expression of miRNAs, and subsequently act on different mRNA targets, playing a role in the development of fibrosis in a wide variety of organs, including the heart, liver, kidneys, and spleen. parenchymal organs, including heart, liver, kidney, and spleen, play important roles in the development of fibrosis. These findings elucidate the intricate involvement of the lncRNA/circRNA-miRNA-mRNA axis in the pathophysiological processes underpinning organ fibrosis, thereby enhancing our comprehension of the onset and progression of this condition. Furthermore, they introduce novel potential therapeutic targets within the realm of ncRNA-based therapeutics, offering avenues for the development of innovative drugs aimed at mitigating or reversing the effects of organ fibrosis.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111430"},"PeriodicalIF":4.4,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307207","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}

引用次数: 0

The promotion of cell proliferation and invasion in cutaneous squamous cell carcinomas after ARNT downregulation is associated with CXCL3 ARNT 下调后对皮肤鳞状细胞癌细胞增殖和侵袭的促进作用与 CXCL3 有关。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-09-21 DOI: 10.1016/j.cellsig.2024.111432

Zhan-Yan Pan , Da-Ke Dong , Zhi-Nan Shi , Hui-Jie Yuan , Qiong Wu , Ting-Ting Hu , Xiao-Hui Mo , Qiang Ju

{"title":"The promotion of cell proliferation and invasion in cutaneous squamous cell carcinomas after ARNT downregulation is associated with CXCL3","authors":"Zhan-Yan Pan , Da-Ke Dong , Zhi-Nan Shi , Hui-Jie Yuan , Qiong Wu , Ting-Ting Hu , Xiao-Hui Mo , Qiang Ju","doi":"10.1016/j.cellsig.2024.111432","DOIUrl":"10.1016/j.cellsig.2024.111432","url":null,"abstract":"<div><div>The aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor associated with adaptive responses to cellular stress. Its role in cutaneous squamous cell carcinoma (cSCC) remains poorly understood. The aim of this study was to investigate the role of ARNT in cSCC. Immunohistochemistry revealed downregulation of ARNT in cSCC, precancerous lesions (actinic keratosis), and cells. Knockdown of ARNT in A431 and SCL-1 cells significantly enhanced cell growth and metastasis. Microarray analysis and Ingenuity Pathway Analysis confirmed that loss of ARNT in A431 cells was highly correlated with cell growth and movement and upregulated CXCL3 expression. Cellular and xenograft experiments further confirmed that ARNT regulates cSCC proliferation and invasiveness in a CXCL3-dependent manner. ARNT may regulate CXCL3 expression through ROS-STAT3 pathway. In conclusion, this study demonstrates that ARNT plays a critical role in the development of cSCC and significantly affects the proliferation and metastatic ability of cSCC cells. It has the potential to serve as an ideal treatment target for cSCC.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111432"},"PeriodicalIF":4.4,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307208","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}

引用次数: 0

Disrupting the protein-protein interaction network of Hsp72 inhibits adipogenic differentiation and lipid synthesis in adipocytes 破坏Hsp72的蛋白-蛋白相互作用网络可抑制脂肪细胞的成脂分化和脂质合成。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-09-21 DOI: 10.1016/j.cellsig.2024.111431

Yu-Tao Hu , Yu-Wei Lin , Shi-Yao Guo , Zhi Jiang , Shu-Min Xu , Zheng Su , Jin-Ming Zhang , Yong Rao , Shuo-Bin Chen , Zhi-Shu Huang

{"title":"Disrupting the protein-protein interaction network of Hsp72 inhibits adipogenic differentiation and lipid synthesis in adipocytes","authors":"Yu-Tao Hu , Yu-Wei Lin , Shi-Yao Guo , Zhi Jiang , Shu-Min Xu , Zheng Su , Jin-Ming Zhang , Yong Rao , Shuo-Bin Chen , Zhi-Shu Huang","doi":"10.1016/j.cellsig.2024.111431","DOIUrl":"10.1016/j.cellsig.2024.111431","url":null,"abstract":"<div><div>The biological function against obesity of heat shock protein Hsp72 in adipose tissue has remained unclear. Our findings demonstrated that the expression levels of Hsp72 increased during the triglyceride (TG) accumulation process both in adipose tissue and 3T3-L1 cells. A significant decrease in adipogenic gene expression and TG levels was observed upon Hsp72 knockdown in 3T3-L1 cells, suggesting that Hsp72 promoted adipogenic differentiation and lipid synthesis processes. Encouraged by these findings, we further confirmed the allosteric Hsp72 inhibitor<strong>s YK5</strong> and <strong>MKT-077</strong> also exhibited inhibition of both these processes. Further evaluation revealed that Hsp72 played a key role in interacting with numerous novel metabolic and cytomorphologic-related client proteins, thereby mediating the adipogenesis and lipogenesis process. Hsp72 inhibitors had the potential to disrupt these interactions, leading to the downregulation of adipogenic and lipogenic gene expression, as well as the suppression of TG accumulation. These findings suggested that inhibiting Hsp72 to disrupt adipogenic differentiation and lipid synthesis in adipocytes may be a promising anti-obesity strategy.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111431"},"PeriodicalIF":4.4,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307206","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}

引用次数: 0

The JNK-associated leucine zipper protein exerts a protective effect on renal parenchymal injury by limiting the inflammatory secretome in tubular cells JNK相关亮氨酸拉链蛋白通过限制肾小管细胞中的炎症分泌组对肾实质损伤起到保护作用。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-09-20 DOI: 10.1016/j.cellsig.2024.111428

Chen Li , Xiaofei Wang , Maoqing Tian , Meng Zhang , Xin Zhang , Qiang Fu , Lunzhi Liu , Lu Zhang , Huiming Wang

{"title":"The JNK-associated leucine zipper protein exerts a protective effect on renal parenchymal injury by limiting the inflammatory secretome in tubular cells","authors":"Chen Li , Xiaofei Wang , Maoqing Tian , Meng Zhang , Xin Zhang , Qiang Fu , Lunzhi Liu , Lu Zhang , Huiming Wang","doi":"10.1016/j.cellsig.2024.111428","DOIUrl":"10.1016/j.cellsig.2024.111428","url":null,"abstract":"<div><div>JNK-associated leucine zipper protein (JLP) is a newly identified renal endogenous anti-fibrotic factor that is selectively enriched in renal tubular epithelial cells (TECs). The loss of JLP by TECs is a landmark event that heralds the progression of kidney fibrosis. JLP deficiency ensues a series of pathogenetic cellular processes that are conducive to fibrotic injury. Inflammatory injury is functionally relevant in fibrotic kidneys, and TECs play an essential role in fueling inflammation through aberrant secretions. It is speculated that the loss of JLP in TECs is associated with the relentless inflammation during the development of kidney fibrosis. This study examined the alteration of a panel of inflammatory signatures in TECs under kidney fibrotic circumstances using a <em>Jlp</em> gene-modified unilateral ureteral obstruction (UUO) mouse model or cultured HK-2 cells. It was found that a deficiency of JLP in TECs led to a significant increase in the secretion of inflammatory cytokines including interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), and monocyte chemotactic protein-1 (MCP-1), overactivation of the nuclear factor (NF)-κB/c-Jun N-terminal kinase (JNK) pathway, as well as nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis in response to pro-fibrotic damage. Additionally, the absence of JLP resulted in enhanced macrophage migration and fibroblast activation as paracrine effects elicited by injured TECs. In conclusion, the loss of JLP in TECs catalyses inflammatory injuries in the development of kidney fibrosis.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111428"},"PeriodicalIF":4.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281007","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}

引用次数: 0

TAF1D promotes tumorigenesis and metastasis by activating PI3K/AKT/mTOR signaling in clear cell renal cell carcinoma TAF1D 通过激活透明细胞肾细胞癌中的 PI3K/AKT/mTOR 信号促进肿瘤发生和转移。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-09-20 DOI: 10.1016/j.cellsig.2024.111425

Xuan Hu , Liang Chen , Tao Liu , Ziyu Wan, Hua Yu, Feng Tang, Jiageng Shi, Zhizhuang Chen, Xinghuan Wang, Zhonghua Yang

{"title":"TAF1D promotes tumorigenesis and metastasis by activating PI3K/AKT/mTOR signaling in clear cell renal cell carcinoma","authors":"Xuan Hu , Liang Chen , Tao Liu , Ziyu Wan, Hua Yu, Feng Tang, Jiageng Shi, Zhizhuang Chen, Xinghuan Wang, Zhonghua Yang","doi":"10.1016/j.cellsig.2024.111425","DOIUrl":"10.1016/j.cellsig.2024.111425","url":null,"abstract":"<div><div>Clear cell renal cell carcinoma (ccRCC) is a malignant tumor needs more effective treatments. TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D) is a member of the selective factor 1 complex and functions in RNA polymerase I-dependent transcription. Higher TAF1D expression was found in ccRCC tumor tissues and indicated worse survival. Our study aimed to investigate the therapeutic potential of TAF1D in ccRCC. The proliferation and migration of ccRCC cells were significantly inhibited after TAF1D knockdown, while TAF1D overexpressing had opposite effects. Moreover, TAF1D knockdown induced cells to undergo G<sub>0</sub>/G<sub>1</sub> cell cycle arrest and blockade of the epithelial-mesenchymal transition (EMT) process. Mechanistically, TAF1D affect the cell cycle and EMT through the PI3K/AKT/mTOR signaling pathway, thereby promoting the proliferation and metastasis of ccRCC cells in vivo and in vitro. The inhibitory effect of TAF1D knockdown could be reverted by the AKT activator SC79 in ccRCC cells, confirming this mechanism. Besides, TAF1D knockdown in ccRCC cells had a sensitizing effect on sunitinib and enhanced tumor cell inhibiting induced by sunitinib. In conclusion, TAF1D may be a promising target for the treatment of ccRCC and for overcoming sunitinib resistance.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111425"},"PeriodicalIF":4.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281006","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}

引用次数: 0