Cellular signalling最新文献

{"title":"Unveiling the role of MDH1 in breast cancer drug resistance through single-cell sequencing and schottenol intervention","authors":"Jian Lu ,&nbsp;Feng Ding ,&nbsp;Yongjie Sun ,&nbsp;Yu Zhao ,&nbsp;Wenbiao Ma ,&nbsp;Huan Zhang ,&nbsp;Bo Shi","doi":"10.1016/j.cellsig.2025.111608","DOIUrl":"10.1016/j.cellsig.2025.111608","url":null,"abstract":"<div><div>This study utilizes single-cell RNA sequencing data to reveal the transcriptomic characteristics of breast cancer and normal epithelial cells. Nine significant cell populations were identified through stringent quality control and batch effect correction. Further classification of breast cancer epithelial cells based on the PAM50 method and clinical subtypes highlighted significant heterogeneity between triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (NTNBC). The study also analyzed myeloid cells and tumor-infiltrating lymphocytes (TILs) within the breast cancer immune microenvironment, identifying 14 TIL subpopulations and assessing their proportion variations across different patients. The CellChat tool revealed a complex cellular communication network within the tumor microenvironment, showing notable differences in communication intensity and patterns between TNBC and NTNBC patients. Additionally, the key regulatory role of the senescence-associated gene MDH1 in breast cancer was confirmed, and its impact on drug sensitivity was explored. Finally, it was discovered that the phytosterol Schottenol inhibits breast cancer cell proliferation by downregulating MDH1 expression and enhances sensitivity to paclitaxel. These findings provide new insights into MDH1 as a therapeutic target and suggest Schottenol as a potential strategy to overcome breast cancer drug resistance.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111608"},"PeriodicalIF":4.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001000","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 PLAC1 as a prognostic biomarker and molecular target in clear cell renal cell carcinoma","authors":"Ying Kong ,&nbsp;Zongming Jia ,&nbsp;Yizhang Sun ,&nbsp;Lichen Jin ,&nbsp;Tong Zhang ,&nbsp;Qiya Xu ,&nbsp;Yuhua Huang","doi":"10.1016/j.cellsig.2025.111606","DOIUrl":"10.1016/j.cellsig.2025.111606","url":null,"abstract":"<div><div>Clear cell renal cell carcinoma (ccRCC) is a common clinical tumor of the urinary system. The lack of effective diagnostic and treatment options poses a serious challenge to clinical treatment. Therefore, identifying effective molecular targets has become one of the potential means to treat this disease. Firstly, the analysis of the TCGA database found that PLAC1 was abnormally highly expressed in ccRCC and was negatively correlated with patient prognosis. Western blotting and immunofluorescence experiments further verified that PLAC1 was highly expressed in ccRCC patients, and knockdown of PLAC1 inhibited the development of ccRCC <em>in vitro</em>. Last, high-throughput virtual screening technology (HTVS) was performed to identify two molecular inhibitors ，AmB and Cana, which were able to reduce the expression of PLAC1 and inhibited the progression of ccRCC. In conclusion, the current investigation indicated that the PLAC1 could serve as a prognostic biomarker, and AmB and Cana inhibit the progression of ccRCC by reducing PLAC1, making it a potential therapeutic option for ccRCC.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111606"},"PeriodicalIF":4.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000994","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 “The role of α7nAchR and PD-L1 in neuroimmune regulation of keloid treatment” [Cellular Signalling, Volume 121 (2024), Article 111275]","authors":"Zucheng Luo ,&nbsp;Shaoluan Zheng ,&nbsp;Jiaqi Liu ,&nbsp;Fazhi Qi","doi":"10.1016/j.cellsig.2025.111599","DOIUrl":"10.1016/j.cellsig.2025.111599","url":null,"abstract":"","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111599"},"PeriodicalIF":4.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982241","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":"Aquaporin-5 facilitates liver regeneration following hepatectomy via ROS/GSDMD pathway","authors":"Bin Li ,&nbsp;Guohu Di ,&nbsp;Huanhuan Ge ,&nbsp;Peirong Song ,&nbsp;Wenshuo Han ,&nbsp;Hetong Sun ,&nbsp;Dianqiang Wang ,&nbsp;Peng Chen ,&nbsp;Ye Wang","doi":"10.1016/j.cellsig.2025.111602","DOIUrl":"10.1016/j.cellsig.2025.111602","url":null,"abstract":"<div><div>During the proliferative phase of liver regeneration, insufficient regulation of hepatocyte hydrogen peroxide (H₂O₂) overproduction can result in oxidative stress and hepatocyte death. This study aims to investigate the influence of Aquaporin 5 (Aqp5) on liver regeneration by evaluating its role in reactive oxygen species (ROS) generation and NLRP3-GSDMD-mediated pyroptosis. A 70 % partial hepatectomy (PHx) model was established in Aqp5^−/− mice to evaluate the pathological changes in the liver. Reactive oxygen species (ROS) production was assessed using a dichlorodihydrofluorescein diacetate (DCFH-DA) assay. Aqp5 deficiency significantly increased ROS production, the number of TUNEL-positive cells, and disrupted mitochondrial membrane potential in the liver of Aqp5-deficient mice. The impact of Aqp5 on ROS/NLRP3/Gasdermin-D (GSDMD)-mediated pyroptosis was examined through the administration of <em>N</em>-acetyl-L-cysteine (NAC, an ROS scavenger) or disulfiram (DSF, a GSDMD inhibitor). In Aqp5-deficient mice, the regenerative liver exhibited increased expression of NLRP3, enhanced activation of caspase-1 and GSDMD, as well as elevated secretion of IL-1β. Treatment with DSF significantly attenuated GSDMD-mediated pyroptosis triggered by Aqp5 deficiency in the regenerating liver. Furthermore, the administration of NAC to Aqp5-deficient mice resulted in a reduction in the expression levels of NLRP3, the activity levels of caspase-1 and GSDMD, as well as the release of IL-1β. Our findings indicate that the deficiency of Aqp5 facilitates GSDMD activation through the production of ROS. The suppression of ROS or inhibition of GSDMD significantly alleviates the damage and pyroptosis observed in Aqp5-deficient regenerative liver.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111602"},"PeriodicalIF":4.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000991","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":"Corrigendum to “MicroRNA-206 in human cancer: Mechanistic and clinical perspectives” [Cellular Signalling, volume 101, Article 110525]","authors":"Leila Bahari Khasraghi ,&nbsp;Morteza Nouri ,&nbsp;Masoud Vazirzadeh ,&nbsp;Nasrin Hashemipour ,&nbsp;Mehrdad Talebi ,&nbsp;Fatemehsadat Aghaei Zarch ,&nbsp;Jamal Majidpoor ,&nbsp;Kambiz Kalhor ,&nbsp;Poopak Farnia ,&nbsp;Sajad Najafi ,&nbsp;Seyed Mohsen Aghaei Zarch","doi":"10.1016/j.cellsig.2025.111597","DOIUrl":"10.1016/j.cellsig.2025.111597","url":null,"abstract":"","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111597"},"PeriodicalIF":4.4,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969789","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":"Effect of the glucagon-like peptide-1 receptor agonists dulaglutide on kidney outcomes in db/db mice","authors":"Fengyi Deng ,&nbsp;Ping Zhang ,&nbsp;Huaiyun Li ,&nbsp;Xingyu Fan ,&nbsp;Yijun Du ,&nbsp;Xing Zhong ,&nbsp;Nuojin Wang ,&nbsp;Meiwen He ,&nbsp;Yue Wang ,&nbsp;Tianrong Pan","doi":"10.1016/j.cellsig.2025.111603","DOIUrl":"10.1016/j.cellsig.2025.111603","url":null,"abstract":"<div><div>Diabetic kidney disease (DKD), a microvascular complication of diabetes mellitus, represents a significant clinical challenge. This study investigated the reno-protective effects of dulaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) widely used in the management of diabetes, and aimed to elucidate its underlying mechanisms. Mice with db/db and db/m genotypes were allocated into four experimental groups and treated with either dulaglutide or a saline control for 10 weeks. Following the treatment period, biological samples were collected for comprehensive analysis. Serum and urinary creatinine levels were measured using a creatinine assay, while urinary protein concentrations were quantified via ELISA. Histopathological kidney damage was assessed through hematoxylin and eosin (HE) staining, with glomerular lesions evaluated using periodic acid-Schiff (PAS) staining. Inflammatory markers, ferroptosis-related indicators, and fibrosis in kidney tissues were further analyzed through PCR, Western blot (WB), immunohistochemistry (IHC), and transmission electron microscopy (TEM). Consistent with prior findings, this research demonstrated that dulaglutide improves renal function and mitigates pathological kidney damage in db/db mice. Treatment with dulaglutide significantly reduced mRNA expression of ferroptosis-related markers, including ACSL4, SLC7A11, and Ptgs2, alongside a decrease in 4-HNE levels in kidney tissues. Furthermore, dulaglutide downregulated ACSL4 protein levels and upregulated GPX4 protein expression, thereby ameliorating mitochondrial damage in renal tubular cells. In addition to these effects, dulaglutide alleviated kidney inflammation and fibrosis in db/db mice, with concomitant suppression of P-STAT3 and P-ERK expression. Collectively, these findings underscore dulaglutide's reno-protective effects in DKD, mediated through the inhibition of inflammation, improvement in renal fibrosis and ferroptosis, and modulation of P-STAT3 and P-ERK signaling pathways.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111603"},"PeriodicalIF":4.4,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977881","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 emerging landscape of small nucleolar RNA host gene 10 in cancer mechanistic insights and clinical relevance","authors":"Jingyu Zhu ,&nbsp;Zihao Jian ,&nbsp;Fangteng Liu ,&nbsp;Lulu Le","doi":"10.1016/j.cellsig.2025.111590","DOIUrl":"10.1016/j.cellsig.2025.111590","url":null,"abstract":"<div><div>Small nucleolar RNA host gene 10 (SNHG10) is a newly recognized long non-coding RNA (lncRNA) with significant implications in cancer biology. Abnormal expression of SNHG10 has been observed in various solid tumors and hematological malignancies. Research conducted in vivo and in vitro has revealed that SNHG10 plays a pivotal role in numerous biological processes, including cell proliferation, apoptosis, invasion and migration, drug resistance, energy metabolism, immune evasion, as well as tumor growth and metastasis. SNHG10 regulates tumor development through several mechanisms, such as competing with microRNA (miRNA) for binding sites, modulating various signaling pathways, influencing transcriptional activity, and affecting epigenetic regulation. The diverse biological functions and intricate mechanisms of SNHG10 highlight its considerable clinical relevance, positioning it as a potential pan-cancer biomarker and therapeutic target. This review aims to summarize the role of SNHG10 in tumorigenesis and cancer progression, clarify the molecular mechanisms at play, and explore its clinical significance in cancer diagnosis and prognosis prediction, along with its therapeutic potential.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111590"},"PeriodicalIF":4.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969822","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":"NSD2 mediated H3K36me2 promotes pulmonary arterial hypertension by recruiting FOLR1 and metabolism reprogramming","authors":"Zhi-bo Liu ,&nbsp;Rong-rong Zhu ,&nbsp;Jin-long Liu ,&nbsp;Qi-rong Xu ,&nbsp;Hua Xu ,&nbsp;Ji-chun Liu ,&nbsp;Xue-liang Zhou","doi":"10.1016/j.cellsig.2025.111594","DOIUrl":"10.1016/j.cellsig.2025.111594","url":null,"abstract":"<div><div>Pulmonary artery hypertension (PAH) is characterized by a cancer-like metabolic shift towards aerobic glycolysis. Nuclear Receptor Binding SET Domain Protein 2 (NSD2), a histone methyltransferase, has been implicated in PAH, yet its precise role remains unclear. In this study, we induced PAH in C57BL/6 mice using monocrotaline (MCT) and observed increased FOLR1 expression in PAH tissues, which was suppressed by NSD2 knockdown. Silencing NSD2 or FOLR1 inhibited the proliferation and migration of pulmonary artery endothelial cells (PAECs) and alleviated PAH phenotypes, right ventricular dysfunction, and pulmonary artery remodeling. Mechanistically, NSD2 knockdown prevented nuclear translocation of FOLR1 and its interaction with H3K36me2. Metabolic analysis revealed that NSD2 or FOLR1 knockdown reversed the increased oxygen consumption rate, extracellular acidification rate, glucose consumption, lactate production, and G6PD activity in MCT-treated PAECs. Furthermore, NSD2 or FOLR1 silencing decreased the expression of key glycolytic genes (HK2, TIGAR, and G6PD) by suppressing their promoter activity and weakening the interaction between FOLR1/H3K36me2 and these gene promoters. Our findings suggest that NSD2-mediated H3K36me2 recruits FOLR1 to promote PAH, and FOLR1 acts as a transcriptional factor to upregulate glycolytic gene expression in PAECs.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111594"},"PeriodicalIF":4.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969790","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":"SEPT5 overexpression predicts poor prognosis and promotes progression through feedback regulation of HIF-1α in clear cell renal cell carcinoma","authors":"Wenjing Liu ,&nbsp;Yueli Ni ,&nbsp;Wenjie Wang ,&nbsp;Kun Cui ,&nbsp;Qiuxin Duan ,&nbsp;Ziyuan Bai ,&nbsp;Asif Shahzad ,&nbsp;Xiangjie Liu ,&nbsp;Yurong Dong ,&nbsp;Zhe Xu ,&nbsp;Jinshan Zhang ,&nbsp;Dongmei Peng ,&nbsp;Zhuoran Teng ,&nbsp;Yanping Gao ,&nbsp;Zhe Yang ,&nbsp;Qiao Zhang","doi":"10.1016/j.cellsig.2025.111591","DOIUrl":"10.1016/j.cellsig.2025.111591","url":null,"abstract":"<div><div>Clear cell renal cell carcinoma (ccRCC), a predominant subtype of renal cell carcinoma, significantly contributes to the heightened morbidity and mortality in individuals diagnosed with urologic tumors. The challenges posed by high malignancy at the initial diagnosis of ccRCC, therapeutic resistance, and unfavorable patient prognosis remain largely unresolved. Our findings indicate that SEPT5 is upregulated in ccRCC and this upregulation is associated with an adverse prognosis for ccRCC patients. Furthermore, we demonstrate that overexpression of SEPT5 promotes proliferation of ccRCC cells, alters their cell cycle distribution, and enhances their migratory and invasive capabilities. Additionally, we observe a positive correlation between SEPT5 overexpression and resistance to sorafenib and sunitinib in ccRCC cells. Further mechanistic investigations have revealed that SEPT5 serves as a novel direct transcriptional target of HIF-1α, leading to subsequent reduction in protein expression and nuclear translocation of HIF-1α. This establishes a feedback loop in ccRCC tumorigenesis. Ultimately, knockdown of SEPT5 significantly inhibits xenografted tumor growth in vivo. Overall, this study provides compelling evidence that directly targeting the HIF-1α-SEPT5 feedback axis may be an effective approach for suppressing the proliferation and progression of ccRCC, offering new insights into the diagnosis and treatment of ccRCC patients.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111591"},"PeriodicalIF":4.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969786","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":"Substrate stiffness modulates osteogenic and adipogenic differentiation of osteosarcoma through PIEZO1 mediated signaling pathway","authors":"Qingyuan Gao ,&nbsp;Meijing Wang ,&nbsp;Xiangyi Hou ,&nbsp;Meiying Li ,&nbsp;Lisha Li","doi":"10.1016/j.cellsig.2025.111601","DOIUrl":"10.1016/j.cellsig.2025.111601","url":null,"abstract":"<div><div>Most osteosarcoma (OS) cases exhibit poor differentiation at the histopathological level. Disruption of the normal osteogenic differentiation process results in the unregulated proliferation of precursor cells, which is a critical factor in the development of OS. Differentiation therapy aims to slow disease progression by restoring the osteogenic differentiation process of OS cells and is considered a new approach to treating OS. However, there are currently few studies on the mechanism of differentiation of OS, which puts the development of differentiation therapeutic drugs into a bottleneck. Substrate stiffness can regulate differentiation in mesenchymal stem cells. Evidence supports that mesenchymal stem cells and osteoblast precursors are the origin of OS. In this study, we simulated different stiffnesses in vitro to investigate the mechanism of substrate stiffness affecting differentiation of OS. We demonstrate that Piezo type mechanosensitive ion channel component 1 (PIEZO1) plays a critical regulatory role in sensing substrate stiffness in osteogenic and adipogenic differentiation of OS. When OS cells are cultured on the stiff substrate, integrin subunit beta 1 (ITGB1) increases and cooperates with PIEZO1 to promote Yes-Associated Protein (YAP) entering the nucleus, and may inhibit EZH2, thereby inhibiting H3K27me3 and increasing RUNX2 expression, and cells differentiate toward osteogenesis. Our results provide new insights for research on differentiation treatment of OS and are expected to help identify new targets for future drug design.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111601"},"PeriodicalIF":4.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969819","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}