Cellular signalling最新文献

{"title":"The emerging role of PANoptosis in viral infections disease","authors":"Xu Cheng ,&nbsp;Taoyuan Zeng ,&nbsp;Yingshu Xu ,&nbsp;Yongai Xiong","doi":"10.1016/j.cellsig.2024.111497","DOIUrl":"10.1016/j.cellsig.2024.111497","url":null,"abstract":"<div><div>PANoptosis is a distinct inflammatory cell death mechanism that involves interactions between pyroptosis, apoptosis, and necroptosis. It can be regulated by diverse PANoptosome complexes built by integrating components from various cell death modalities. There is a rising interest in PANoptosis' process and functions. Viral infection is an important trigger of PANoptosis. Viruses invade host cells through their unique mechanisms and utilize host cell resources for replication and proliferation. In this process, viruses interfere with the normal physiological functions of host cells, including cell death mechanisms. A variety of viruses, such as influenza A virus (IAV), herpes simplex virus 1 (HSV1) and coronaviruses, have been found to induce PANoptosis in host cells. Given the importance of PANoptosis across the disease spectrum, this review briefly describes the relationships between pyroptosis, apoptosis, and necroptosis, highlights the key molecules in PANoptosome formation and activation, and outlines the multifaceted roles of PANoptosis in viral diseases, including potential therapeutic targets. We also talk about key principles and significant concerns for future PANoptosis research. Improved understanding of PANoptosis and its mechanisms is critical for discovering new treatment targets and methods.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"125 ","pages":"Article 111497"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567506","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":"TIFA enhances glycolysis through E2F1 and promotes the progression of glioma","authors":"Zhibing Liu ,&nbsp;Miaolong He ,&nbsp;Zeshun Yu ,&nbsp;Longbo Ma ,&nbsp;Xiuwen Wang ,&nbsp;Fangling Ning","doi":"10.1016/j.cellsig.2024.111498","DOIUrl":"10.1016/j.cellsig.2024.111498","url":null,"abstract":"<div><h3>Objective</h3><div>TRAF interacting protein with forkhead associated domain (TIFA) influence progression of many cancers. However, its role in glioma remains to be explored. This study investigated the function of TIFA in glioma.</div></div><div><h3>Methods</h3><div>The TIFA expression in glioma and patient outcomes were analyzed using online database. Gene set enrichment analysis (GSEA) revealed related mechanisms of TIFA in glioma. TIFA's effects on glioma glycolysis and growth were assessed using in vitro and in vivo experiments. Moreover, luciferase reporter and ChIP were employed to explore the interactions among E2F1, GLUT1, HK2, and LDHA. The subcutaneous xenograft assay further elaborated the effects of TIFA in glioma.</div></div><div><h3>Results</h3><div>We found overexpressed TIFA in glioma. Moreover, the high TIFA expression was associated with poor prognosis of glioma. Furthermore, GSEA indicated that overexpressed TIFA promoted E2F1 and glycolysis. Knockdown of TIFA decreased glioma development in cell and mice. TIFA knockdown down-regulated the expression of E2F1, GLUT1, HK2, and LDHA.</div></div><div><h3>Conclusions</h3><div>The study provides evidence that TIFA regulates E2F1 expression in glioma cells and promotes the proliferation, migration, and glycolysis. TIFA might be an advantageous therapeutic strategy against glioma.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"125 ","pages":"Article 111498"},"PeriodicalIF":4.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557275","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":"eIF3d specialized translation requires a RACK1-driven eIF3d binding to 43S PIC in proliferating SH-SY5Y neuroblastoma cells","authors":"Federica Silvestri ,&nbsp;Raffaele Montuoro ,&nbsp;Elisabetta Catalani ,&nbsp;Francesca Tilesi ,&nbsp;Daniela Willems ,&nbsp;Nicla Romano ,&nbsp;Sara Ricciardi ,&nbsp;Davide Cervia ,&nbsp;Marcello Ceci","doi":"10.1016/j.cellsig.2024.111494","DOIUrl":"10.1016/j.cellsig.2024.111494","url":null,"abstract":"<div><div>Translation initiation of most mammalian mRNAs is mediated by a 5′ cap structure that binds eukaryotic initiation factor 4E (eIF4E). Notably, most mRNAs are still capped when eIF4E is inhibited, suggesting alternative mechanisms likely mediate cap-dependent mRNA translation without functional eIF4F. Here we found that, when eIF4E is inhibited, the ribosomal scaffold RACK1 recruits eIF3d on the 43S pre-initiation complex. Moreover, we found that it is just PKCBII in its active form that promotes the binding of RACK1 to eIF3d. These studies disclose a previously unknown role of ribosomal RACK1 for eIF3d specialized translation.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"125 ","pages":"Article 111494"},"PeriodicalIF":4.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544058","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":"MFGE8 promotes gastric cancer progression by activating the IL-6/JAK/STAT3 signaling","authors":"Long-long Ding ,&nbsp;Meng Zhang ,&nbsp;Tao Zhang ,&nbsp;Hui Liu ,&nbsp;Peng-fei Liu","doi":"10.1016/j.cellsig.2024.111486","DOIUrl":"10.1016/j.cellsig.2024.111486","url":null,"abstract":"<div><h3>Objective</h3><div>Gastric cancer is malignant cancer with high morbidity and mortality worldwide. Milk fat globule EGF and factor V/VIII domain containing (MFGE8) was involved in many cancers. Nevertheless, the role of MFGE8 in gastric cancer remained indistinct. To probe the role of MFGE8 in gastric cancer and further explore the regulating mechanism.</div></div><div><h3>Methods</h3><div>GEPIA was employed for analysis of MFGE8 expression and survival of gastric cancer patients. MFGE8 expression in gastric cancer was determined by immunohistochemistry, PCR, and western blot. The effect of MFGE8 on gastric cancer cells were evaluated by a series of cell function experiments. The mechanism of MFGE8 on gastric cancer was analyzed by GSEA and verified by in vitro and in vivo experiments.</div></div><div><h3>Results</h3><div>MFGE8 was over-expressed in gastric cancer. Silence of MFGE8 suppressed cell viability, proliferated ability, migrated and invasive ability, and EMT, but accelerated cell apoptosis. The opposite results were obtained in MFGE8-overexpressed gastric cancer cells. Zinc finger and BTB domain containing 7 A (ZBTB7A) was a transcription factor of MFGE8. ZBTB7A overexpression eliminated the effect of MFGE8 on gastric cancer cells. MFGE8 activated the IL-6/JAK/STAT3 signaling. Inhibition of IL-6/JAK/STAT3 signaling by Stattic (pathway inhibitor) could eliminate the promoting effect of MFGE8 on IL-6/JAK/STAT3 signaling. In addition, MFGE8 shRNA inhibited tumor growth.</div></div><div><h3>Conclusion</h3><div>MFGE8 promoted cell proliferation, EMT progress, and tumor growth of gastric cancer by activating the IL-6/JAK/STAT3 signaling.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"125 ","pages":"Article 111486"},"PeriodicalIF":4.4,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555000","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":"Epithelial splicing regulatory protein 1 promotes peritoneal dissemination of ovarian cancer by inducing the formation of circular RNAs modulating epithelial plasticity","authors":"Guoqing Li ,&nbsp;Xiaoling Zhou ,&nbsp;Xiaoli Liu ,&nbsp;Lanqing Gong ,&nbsp;Wenhan Li ,&nbsp;Tiantian Shen ,&nbsp;Qiulei Wu ,&nbsp;Xiaoman Wang ,&nbsp;Zehua Wang ,&nbsp;Jing Cai ,&nbsp;Le Chen","doi":"10.1016/j.cellsig.2024.111485","DOIUrl":"10.1016/j.cellsig.2024.111485","url":null,"abstract":"<div><div>Peritoneal metastases prevalently occur in ovarian cancer, deteriorating patient prognosis. During the metastatic cascade, tumor plasticity enables cells to adapt to environmental changes, thereby facilitating dissemination. We previously found that epithelial splicing regulatory protein 1 (ESRP1) is linked to peritoneal metastasis and epithelial-mesenchymal plasticity in ovarian cancer. This study delves into the underlying mechanism. We found that ESRP1 preserves epithelial plasticity in ovarian cancer cells <em>in vitro</em> and <em>in vivo</em>. Functionally, ESRP1 enhances ovarian cancer cell growth and peritoneal dissemination. High-throughput sequencing revealed several ESRP1-related epithelial RNAs, encompassing both linear and circular forms. Specifically, ESRP1 triggers the cyclization of circPAFAH1B2 and circUBAP2 through binding to the GGU sequences in adjacent introns. The two ESRP1-induced circular RNAs stabilize <em>DKK3</em> and <em>AHR</em> mRNAs, which are critical for epithelial plasticity, through interaction with IGF2BP2. Collectively, ESRP1 triggers the formation of circPAFAH1B2 and circUBAP2, which in turn stabilizes <em>DKK3</em> and <em>AHR</em> through IGF2BP2 binding, thereby modulating the epithelial plasticity and aiding the peritoneal spread of ovarian cancer cells. The findings unveiled a biological network, orchestrated by ESRP1, that governs the epithelial-mesenchymal plasticity of ovarian cancer cells, emphasizing the therapeutic potential of ESRP1 and its induced circular RNAs for ovarian cancer treatment.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"125 ","pages":"Article 111485"},"PeriodicalIF":4.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495984","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":"Hsa_circ_0048764 facilitates the progression of non-small cell lung cancer by targeting miR-1178-3p/HMGA1 axis","authors":"Xing Sun ,&nbsp;Ping Feng ,&nbsp;Haihua Chen ,&nbsp;Zhijuan Ji ,&nbsp;Lanmei Zhuang ,&nbsp;Ting Zhu ,&nbsp;Guangling Ji ,&nbsp;Jin Wang","doi":"10.1016/j.cellsig.2024.111484","DOIUrl":"10.1016/j.cellsig.2024.111484","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC) remains a highly lethal disease, with a lack of fully established biomarkers and therapies. Circular RNAs (circRNAs) have emerged as powerful regulators of gene expression in multiple cancers. The role of circRNAs in NSCLC progression is still not well understood. In this study, GEO database analysis and qRT-PCR results revealed that hsa_circ_0048764 (circ_0048764) was overexpressed in NSCLC tissues and associated with poorer overall survival in patients with NSCLC. Functional assays demonstrated that silencing circ_0048764 inhibited NSCLC cell proliferation and metastasis. Bioinformatics analysis identified miR-1178-3p as having complementary binding sites with circ_0048764, a finding further validated by the dual-luciferase reporter assay. Additionally, predictions from the Starbase3.0 database, along with cellular experiments, revealed that miR-1178-3p regulates HMGA1 expression in NSCLC. Taken together, our findings suggest that circ_0048764 promotes NSCLC progression by enhancing HMGA1 expression through sponging miR-1178-3p, offering potential therapeutic targets for NSCLC treatment.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"125 ","pages":"Article 111484"},"PeriodicalIF":4.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495985","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":"The SIRT6/BAP1/xCT signaling axis mediates ferroptosis in cisplatin-induced AKI","authors":"Songyuan Yang ,&nbsp;Lijia Chen ,&nbsp;Shikuan Din ,&nbsp;Zehua Ye ,&nbsp;Xiangjun Zhou ,&nbsp;Fan Cheng ,&nbsp;Wei Li","doi":"10.1016/j.cellsig.2024.111479","DOIUrl":"10.1016/j.cellsig.2024.111479","url":null,"abstract":"<div><h3>Background</h3><div>Cisplatin is extensively utilized in clinical settings for treating solid tumors; However, its use is restricted because of the kidney damage caused by side effects. Moreover, currently, no effective medications have been approved to prevent or treat acute kidney injury induced by cisplatin. Our research indicates that sirtuin 6 (SIRT6) can inhibit ferroptosis induced by cisplatin, and the use of SIRT6 agonists can alleviate acute kidney injury caused by cisplatin.</div></div><div><h3>Methods</h3><div>An animal model of cisplatin-induced acute kidney injury (AKI) was established, followed by RNA sequencing to identify potential differentially expressed genes (DEGs) and associated pathways. To explore the role of SIRT6 in this model, SIRT6 knockout mice were generated, and recombinant adeno-associated virus was employed to achieve SIRT6 overexpression in the mice. In vitro, cells were cultured in a cisplatin-containing medium to establish a cisplatin-induced cell model. The function of SIRT6 was further investigated by overexpressing or knocking down the gene using lentiviral plasmids. To elucidate the underlying molecular mechanisms, we employed RNA sequencing, performed bioinformatics analyses, and conducted chromatin immunoprecipitation assays.</div></div><div><h3>Results</h3><div>RNA sequencing and Western blot analyses revealed a significant reduction in SIRT6 expression in mice with cisplatin-induced acute kidney injury (AKI). Enhancing SIRT6 expression improved renal function, reduced ferroptosis, and mitigated kidney damage, whereas SIRT6 knockout exacerbated kidney injury and heightened ferroptosis. Mechanistically, RNA sequencing, bioinformatics analysis, and chromatin immunoprecipitation assays demonstrated that SIRT6 inhibits ferroptosis by reducing the acetylation of histone H4K9ac at the BAP1 promoter. Furthermore, in vitro studies demonstrated that the SIRT6 agonist UBCS039 can alleviate cisplatin-induced acute kidney injury, highlighting its potential therapeutic role in mitigating cisplatin's damaging effects. However, further research is needed to fully elucidate the underlying mechanisms and to validate these findings in vivo.</div></div><div><h3>Conclusion</h3><div>Our findings underscore the critical role of the SIRT6/BAP1/xCT axis in regulating ferroptosis, particularly via the downregulation of SIRT6, in the context of cisplatin-induced acute kidney injury (AKI). This suggests that SIRT6 could be a promising therapeutic target for treating cisplatin-induced AKI. However, additional research is required to explore the specific mechanisms and fully assess the therapeutic potential of SIRT6 in this context.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"125 ","pages":"Article 111479"},"PeriodicalIF":4.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495989","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":"The BET inhibitor JQ1 suppresses tumor survival by ABCB5-mediated autophagy in uveal melanoma","authors":"Weiqin Liu ,&nbsp;Zedu Cui ,&nbsp;Qi Wan ,&nbsp;Ying Liu ,&nbsp;Minghao Chen ,&nbsp;Yaqi Cheng ,&nbsp;Xuan Sang ,&nbsp;Yaru Su ,&nbsp;Simin Gu ,&nbsp;Chaoyang Li ,&nbsp;Chang Liu ,&nbsp;Shuxia Chen ,&nbsp;Zhichong Wang ,&nbsp;Xiaoran Wang","doi":"10.1016/j.cellsig.2024.111483","DOIUrl":"10.1016/j.cellsig.2024.111483","url":null,"abstract":"<div><div>Uveal melanoma (UM), the most common adult ocular tumor, is aggressive and resistant to treatment, posing threat to patients' lives. The novel, effective therapies and the exploration of chemosensitizer for UM are imperative. The anticancer efficacy was evaluated with and without JQ1 treatment or <em>ABCB5</em> gene silencing or overexpression. RNA sequencing identified downstream effectors in JQ1-treated cells. Integrated analysis of The Cancer Genome Atlas data (TCGA) and immunohistochemistry (IHC) revealed the oncogenic role of <em>ABCB5</em>. Functional analyses of JQ1 and defective <em>ABCB5</em> were conducted using flow cytometry, transmission electron microscopy (TEM), IHC and western blot. The effects of JQ1 were validated in a heterotopic tumor model derived from OCM-1 cells. JQ1 inhibited cell proliferation, migration and invasion, induced cell cycle arrest and promoted apoptosis. JQ1 also suppressed the survival of UM in heterotopic tumor model. RNA sequencing indicated that JQ1 down-regulated the expressions of <em>ABCB5</em> and autophagy-related genes, which was confirmed <em>in vitro</em> and <em>in vivo</em> by western blot. <em>ABCB5</em>, a marker associated with cancer stem cells and chemo-resistance, exhibited heightened expression in UM tissues, linked to immune infiltration. Notably, disrupting <em>ABCB5</em> expression impeded UM cell proliferation and interfered with autophagy. Moreover, the overexpression of <em>ABCB5</em> promoted cell proliferation, migration and invasion, and rescued autophagy related gene expression. Of note, JQ1 enhanced the sensitivity of OCM-1 cells to chemotherapy. Thus JQ1 inhibits UM survival <em>via ABCB5</em>-mediated autophagy and enhances chemo-sensitivity, suggesting potential for BET-based approaches in UM clinical management.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"125 ","pages":"Article 111483"},"PeriodicalIF":4.4,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495986","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":"Decreased Mrpl42 expression exacerbates myocardial ischemia and reperfusion injury by inhibiting mitochondrial translation","authors":"Xiaomeng Zhang ,&nbsp;Xiaoqian Chang ,&nbsp;Jingyu Deng ,&nbsp;Congye Li,&nbsp;Yuan Li,&nbsp;Yangzhi Zheng,&nbsp;Rongjin Yang,&nbsp;Xiaoming Xu,&nbsp;Wenjun Yan,&nbsp;Fuyang Zhang,&nbsp;Yunlong Xia,&nbsp;Huishou Zhao,&nbsp;Pingping Xing,&nbsp;Guigao Guo,&nbsp;Fengyue Ding,&nbsp;Ling Tao,&nbsp;Shan Wang","doi":"10.1016/j.cellsig.2024.111482","DOIUrl":"10.1016/j.cellsig.2024.111482","url":null,"abstract":"<div><div>Mammalian mitochondrial DNA (mtDNA) encodes a total of 13 proteins, all of which are subunits of enzyme complexes of the oxidative phosphorylation. The mtDNA-encoded protein synthesis depends on the mitochondrial ribosomal proteins (MRPs), which assemble to form a specialized form of ribosome. Some mtDNA-encoded proteins have been reported to be reduced after myocardial ischemic injury. However, the molecular mechanisms responsible for this decrease and whether this decrease is involved in myocardial ischemia/reperfusion (I/R) injury remains unknown. Here, we found that the mtDNA-encoded protein levels were significantly decreased after I/R injury, while the mRNA levels of these genes were either increased or had no significant change. Subsequently, by querying and analyzing public database resources, we found that the expression of many mitochondrial translation-related proteins tended to decrease after myocardial infarction injury, and the reduction in the expression of these proteins was most obvious for Mrpl42. Furthermore, we found that cardiac Mrpl42 knockdown aggravated I/R-induced cardiac contractile dysfunction and cardiomyocyte death, while restoring Mrpl42 expression in the heart reduced I/R injury. Mrpl42 knockdown impaired the translation of mtDNA-encoded genes, ultimately led to aberrations in mitochondrial morphology and respiratory function. In addition, we found that the decrease in the expression of Mrpl42 after I/R injury was caused by the downregulation of Nrf2, which directly regulates Mrpl42 transcription. Our study revealed that ischemic downregulation of Mrpl42 expression and subsequent inhibition of mitochondrial translation contribute to cardiac I/R injury. Targeting Mrpl42 may be a novel therapeutic intervention for cardiac I/R injury and myocardial infarction.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"125 ","pages":"Article 111482"},"PeriodicalIF":4.4,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496068","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":"PYGB targeted by androgen receptor contributes to tumor progression and metabolic reprogramming in esophageal squamous carcinoma","authors":"Huikai Miao ,&nbsp;Chunmei Xu ,&nbsp;Wuyou Gao ,&nbsp;Leqi Zhong ,&nbsp;Hongmu Li ,&nbsp;Zhesheng Wen ,&nbsp;Qiannan Ren ,&nbsp;Youfang Chen","doi":"10.1016/j.cellsig.2024.111481","DOIUrl":"10.1016/j.cellsig.2024.111481","url":null,"abstract":"<div><h3>Background</h3><div>The incidence and mortality rates of esophageal squamous cell carcinoma (ESCC) are conspicuously augmented in men in contrast to women. The androgen receptor (AR), prevalently associated with the manifestation of male characteristics, is regarded as a pivotal determinant in tumor progression. Nevertheless, its exact role in ESCC remains insufficiently delineated.</div></div><div><h3>Methods</h3><div>In this study, we probed the expression levels of AR and glucose metabolism enzymes in ESCC tissues by means of immunohistochemistry. We exploited chromatin immunoprecipitation and dual luciferase reporter assays to delve into the transcriptional regulatory interrelationships between AR and these enzymes. A gamut of molecular techniques—including multi-omics sequencing, colony formation assays, cell counting kit 8 (CCK8), 5-Ethynyl-2′-deoxyuridine (EdU) incorporation assays, wound-healing assays, transwell migration assays, extracellular acidification rate (ECAR) measurements, lipid droplet fluorescence imaging, and xenograft models—were enlisted to illuminate the functions of these enzymes within ESCC cells.</div></div><div><h3>Results</h3><div>Our discoveries manifested that AR expression was strikingly higher in male ESCC tissues than in their female counterparts. Significantly, we discerned that glycogen phosphorylase B (PYGB), a cardinal enzyme implicated in glucose metabolism, demonstrated not only a positive correlation with AR expression but also an association with adverse prognostic outcomes for ESCC patients. Moreover, AR directly binds to the promoter region of the PYGB gene, thereby potentiating its transcriptional activity. This upregulation of PYGB was ascertained to facilitate proliferation, invasion, and metastasis among ESCC cells while intensifying glycolysis and modifying lipid metabolism pathways within these cells. In animal models employing nude mice, elevated PYGB levels were witnessed to expedite subcutaneous tumor growth as well as lung metastasis.</div></div><div><h3>Conclusions</h3><div>Collectively, our study establishes PYGB as a direct target of AR that assumes an indispensable role in both tumor progression and metabolic reprogramming affiliated with ESCC, thus paving novel avenues for therapeutic strategies centered on metabolic intercessions.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111481"},"PeriodicalIF":4.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495988","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}