Cellular signalling最新文献

{"title":"ANXA2 knockdown inhibits oxidative stress and pyroptosis to alleviate epilepsy by suppressing the toll-like receptor (TLR) pathway","authors":"Fen Wang ,&nbsp;Jiaomei Jiang,&nbsp;Ting Xu,&nbsp;Yongmin Ding","doi":"10.1016/j.cellsig.2025.112140","DOIUrl":"10.1016/j.cellsig.2025.112140","url":null,"abstract":"<div><h3>Objective</h3><div>Epilepsy (EP), characterized by recurrent unprovoked seizures, affects over 50 million individuals globally and imposes substantial socioeconomic and healthcare burdens. We aim to investigate the mechanism by which Annexin A2 (ANXA2) regulates epileptic seizures.</div></div><div><h3>Methods</h3><div>Differentially expressed genes related to EP were identified from GSE73878 and GSE88992 datasets. ANXA2 was identified as a key hub gene through protein-protein interaction (PPI) network analysis. The oxidative stress indicators and inflammatory cytokines were measured by enzyme-linked immunosorbent assay. The proteins related to pyroptosis and pathways were detected by western blot. The role of ANXA2 in kainic acid (KA)-induced hippocampal neurons was evaluated by detecting viability and apoptosis. EP in rats was induced by lithium chloride combined with pilocarpine. The effect of ANXA2 on EP rats was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling, hematoxylin and eosin, and Nissl staining.</div></div><div><h3>Results</h3><div>ANXA2 was identified as a key hub gene related to EP with high predictive value, which was upregulated in KA-induced hippocampal neurons. In vitro, ANXA2 knockdown inhibited oxidative stress, pyroptosis, and apoptosis, while promoting cell viability. Additionally, ANXA2 knockdown reduced oxidative stress, pyroptosis, and epileptic seizures in EP rats. Moreover, ANXA2 knockdown inhibited the toll-like receptor (TLR) pathway in EP rats. Specifically, the activation of the TLR pathway reversed the protective effect of ANXA2 knockdown on both KA-induced hippocampal neurons and EP rats.</div></div><div><h3>Conclusion</h3><div>ANXA2 knockdown mitigates EP by reducing oxidative stress and pyroptosis via suppressing the TLR pathway, highlighting its potential as a therapeutic target for EP treatment.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"136 ","pages":"Article 112140"},"PeriodicalIF":3.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102769","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":"Rab27b-mediated CAFs derived exosomal miR-22-3p suppresses ferroptosis and promotes cisplatin resistance in osteosarcoma","authors":"Wenyuan Duan ,&nbsp;Xiaoying Niu ,&nbsp;Yunsong Liu ,&nbsp;Wen Tian","doi":"10.1016/j.cellsig.2025.112125","DOIUrl":"10.1016/j.cellsig.2025.112125","url":null,"abstract":"<div><div>Chemoresistance remains a significant hurdle in the cisplatin treatment of osteosarcoma, with poor patient outcomes. Cancer-associated fibroblasts (CAFs) and exosomes play crucial roles in this resistance by transferring miRNAs to cancer cells. In this study, we investigated the biological role of CAFs derived exosomal miR-22-3p in promoting chemoresistance. Using single-cell analysis and tissue exosome miRNAs sequencing, CAFs derived exosomal miR-22-3p was significantly associated with cisplatin resistance. Using various co-culture models, we showed the regulatory function of Rab27b and CAFs derived exosomal miR-22-3p, as well as the inhibitory effect of miR-22-3p on PTEN and ferroptosis. Experiments in vivo validated that CAFs derived exosomal miR-22-3p downregulated ferroptosis and promoted resistance to cisplatin. Overall, our findings suggest that targeting the Rab27b/exosomal miR-22-3p/PTEN/ferroptosis axis could be a promising therapeutic strategy for overcoming chemoresistance in osteosarcoma by providing critical insights into the role of exosome-mediated communication within the tumor microenvironment.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"136 ","pages":"Article 112125"},"PeriodicalIF":3.7,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091296","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":"Acute myeloid leukemia cells induce senescence and adipogenic differentiation of mesenchymal stem cells in a tumor-supportive microenvironment at the same time","authors":"Yanju Li ,&nbsp;Chike Zhang ,&nbsp;Yan Zhang ,&nbsp;Yi Huang ,&nbsp;Xiaoshuang Yuan ,&nbsp;Bo Yang ,&nbsp;Zhixu He ,&nbsp;Yang Liu ,&nbsp;Feiqing Wang","doi":"10.1016/j.cellsig.2025.112136","DOIUrl":"10.1016/j.cellsig.2025.112136","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) actively induces the transformation of a normal hematopoietic niche into a tumor-supportive microenvironment. Among them, Mesenchymal stem cells (MSCs)are closely associated with the genesis and development of AML. MSCs derived from AML patients (AML-MSC) show a senescent state, with possibly biased differentiation ability. However, it remains unclear whether AML-MSC exhibits the dual pathological evolution of both senescence characteristics and lipogenic differentiation bias in the microenvironment at the same time. Thus, this study, by analyzing AML-MSC and MSC co-cultured with tumor cells over a long period， revealed that AML affects the AMPK/SIRT1 signaling pathway, inducing an increase in reactive oxygen species in the microenvironment of MSCs, thereby leading to significantly altered metabolic processes, adipose-biased differentiation capacity, and senescence of MSCs. These findings clarify the mechanism by which AML cells actively contribute to the evolution of the tumor microenvironment, providing a theoretical basis for future dual targeting of supportive ecological niches.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"136 ","pages":"Article 112136"},"PeriodicalIF":3.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079456","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":"HSYA targets the ZBP1–166R site to inhibit MAVS signaling: A potential therapeutic strategy for cerebral ischemia-reperfusion injury","authors":"Hao Sun ,&nbsp;Kai Zhu ,&nbsp;Yuqin Peng ,&nbsp;Xian Zhou ,&nbsp;Dennis Chang ,&nbsp;Ning Wang ,&nbsp;Ping Huang","doi":"10.1016/j.cellsig.2025.112138","DOIUrl":"10.1016/j.cellsig.2025.112138","url":null,"abstract":"<div><h3>Background and purpose</h3><div><em>Z</em>-DNA-binding protein 1 (ZBP1) is a marker of neuroinflammation caused by ischemic stroke. Hydroxylsafflower Yellow A (HSYA), the main active component of safflower, has neuroprotective effects in ischemic stroke. Whether HSYA targets ZBP1 to protect mitochondrial function against cerebral ischemia-reperfusion injury (CIRI) remains unclear.</div></div><div><h3>Methods</h3><div>This study involves lateral ventricle injection of plasmid adeno-associated virus (AAV) targeting the ZBP1 locus in SD rats. The MCAO/R model is established using the line plug method to simulate CIRI. Laser speckle blood flow meter and TTC staining are used to evaluate the model. Behavioral, morphological, and imaging techniques were employed to assess the cerebro-protective effects of HSYA against CIRI. Protein-protein docking and co-immunoprecipitation (CO-IP) experiments confirmed the interaction between ZBP1 and MAVS. Subsequently, an oxygen-glucose deprivation/reoxygenation (OGD/R) model was established in HT22 cells. The levels of inflammatory markers and ATP were measured using ELISA, and the expression of signaling pathway proteins was analyzed by Western blot.</div></div><div><h3>Results</h3><div>The cerebral blood flow in rats with a successfully established model was significantly decreased. HSYA reduces neurobehavioral scores and cerebral indices, improves ZBP1 pathologic distribution, and inhibits cell apoptosis. HSYA significantly enhanced cell viability and markedly decreased the apoptosis rate of cells following oxygen-glucose deprivation/reoxygenation (OGD/R) treatment. Additionally, HSYA enhances mitochondrial function and suppresses inflammatory factor release by down-regulating ZBP1 and MAVS expression while up-regulating TBK1 expression, after MCAO/R injury. The protective effect of HSYA is weakened after ZBP1 site mutation. Moreover, ZBP1 and MAVS exhibit a significant interaction.</div></div><div><h3>Conclusion</h3><div>Our study reveals the mechanism of HSYA resisting MCAO/R may be associated with ZBP1 - A166R locus, and to design new ZBP1 antagonist treatment of various diseases associated with ZBP1 provides a template.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"136 ","pages":"Article 112138"},"PeriodicalIF":3.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079448","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":"YWHAG mediated epithelial-mesenchymal transition facilitates tumor progression and metastatic spread in non-small cell lung cancer","authors":"Kai Liu ,&nbsp;Huiyong Han ,&nbsp;Sha Huang ,&nbsp;Lijiang Song ,&nbsp;Jiuzhou Jiang ,&nbsp;Dawei Zheng","doi":"10.1016/j.cellsig.2025.112139","DOIUrl":"10.1016/j.cellsig.2025.112139","url":null,"abstract":"<div><h3>Background</h3><div>YWHAG, a 14–3-3 protein family member, has been implicated in tumorigenesis, yet its role in lung cancer progression and underlying mechanisms remain poorly understood. This study aimed to elucidate the functional and mechanistic contributions of YWHAG to non-small cell lung cancer (NSCLC).</div></div><div><h3>Methods</h3><div>Multi-omics analyses were performed using TCGA pan-cancer datasets, NSCLC single-cell RNA sequencing (scRNA-seq) data (GSE117570 &amp; GSE148071), and public NSCLC mouse models. Functional validation included in vitro siRNA knockdown and overexpression of YWHAG in NCI-H292 cells, co-immunoprecipitation (Co-IP), immunofluorescence, and pathway activity assays. A lung-specific YWHAG knockout mouse model was generated using AAV5-SPC-Cre, and tumor growth/metastasis were assessed in an orthotopic A549 cell-derived NSCLC model via bioluminescence imaging and histopathology.</div></div><div><h3>Results</h3><div>YWHAG was significantly upregulated across 29 cancer types, including lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), and correlated with poor patient survival. scRNA-seq revealed YWHAG-enriched proliferating epithelial cells (ECs) with elevated EMT activity (EMT_AUC score), marked by upregulation of COL12A1, FN1, and YWHAG. Mechanistically, YWHAG knockdown suppressed EMT (increased E-cadherin, decreased N-cadherin/Vimentin), proliferation, and migration, while overexpression exerted opposite effects. YWHAG interacted with LRRK2 to activate the PI3K/AKT pathway, and LRRK2 overexpression rescued PI3K/AKT suppression post-YWHAG knockdown. In mice, lung-specific YWHAG knockout attenuated tumor growth and metastasis, suppressed EMT markers, and reduced metastatic burden in lung, liver, and skeletal muscle.</div></div><div><h3>Conclusion</h3><div>YWHAG drives NSCLC progression by promoting EMT, proliferation, and metastasis via the LRRK2/PI3K/AKT axis. Its pan-cancer overexpression and prognostic significance highlights YWHAG as a promising therapeutic target in lung cancer.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"136 ","pages":"Article 112139"},"PeriodicalIF":3.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079606","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 critical role of the phosphorylation of STAT3 at Y705 in ALCL-associated NPM-ALK-induced transforming activity","authors":"Xin Lin ,&nbsp;Akira Korai ,&nbsp;Yosuke Nakazawa ,&nbsp;Kenji Tago ,&nbsp;Megumi Funakoshi-Tago","doi":"10.1016/j.cellsig.2025.112128","DOIUrl":"10.1016/j.cellsig.2025.112128","url":null,"abstract":"<div><div>The fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) drives oncogenesis in anaplastic large cell lymphoma (ALCL) by activating signal transducer and activator of transcription 3 (STAT3). NPM-ALK requires its kinase activity to induce STAT3 phosphorylation at tyrosine 705 (Y705) and promotes serine 727 (S727) phosphorylation via JNK activation. However, the role of these modifications in NPM-ALK-driven cellular transformation remains unclear. We herein utilized murine Ba/F3 cells expressing NPM-ALK to investigate the impact of these modifications. STAT3 knockdown, followed by reconstitution with wild-type STAT3 or its mutants (Y705F and S727A) revealed that Y705 phosphorylation was essential for NPM-ALK-mediated transformation. STAT3 knockdown suppressed the expression of NPM-ALK-induced STAT3 target genes (c-Myc, Pim, IL-6, and SOCS3) as well as cell proliferation, tumor formation, and spleen, liver, and lymph node enlargement. These effects were restored upon reconstitution with wild-type STAT3 or the S727A mutant, but not the Y705F mutant, confirming the essential role of Y705 phosphorylation in these biological processes. Additionally, wild-type and mutant STAT3 proteins exhibited differential stability, with Y705F being less stable and S727A being more stable. Lysosomal inhibition by bafilomycin A1 increased the expression of wild-type STAT3 and the Y705F mutant, but had no effect on the S727A mutant. Cycloheximide chase assays further confirmed that S727 phosphorylation regulated STAT3 degradation via the lysosomal pathway. These results identify a novel NPM-ALK-induced oncogenic mechanism mediated by STAT3 phosphorylation, highlighting potential therapeutic targets for ALCL.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"136 ","pages":"Article 112128"},"PeriodicalIF":3.7,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074524","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":"YAP regulates the hypertrophy and apoptosis of antler chondrocytes through maintaining calcium homeostasis and mitochondrial function","authors":"Bai-Yu Li ,&nbsp;Zhan-Qing Yang ,&nbsp;Yin-Fei Xing,&nbsp;Qiao-Ling Zhang,&nbsp;Chen-Hao Wang,&nbsp;Zhan-Peng Yue,&nbsp;Bin Guo","doi":"10.1016/j.cellsig.2025.112137","DOIUrl":"10.1016/j.cellsig.2025.112137","url":null,"abstract":"<div><div>YAP is required for chondrogenesis and endochondral bone formation, but its effect on the hypertrophy and apoptosis of antler chondrocytes remains unclear. The present study revealed that YAP was abundantly expressed in antler chondrocytes. Inactivation of YAP restrained the hypertrophy of antler chondrocytes and facilitated chondrocyte apoptosis. Further analysis indicated that blockage of YAP induced the accumulation of cytosolic Ca²⁺ by enhancing the stability of IP3R1/2 mRNA dependent on YTHDF2, that had been identified as a direct downstream target of YAP/TEAD. Meanwhile, attenuation of YAP activated the cytosolic Ca²⁺-mediated PPP3R1/NFATC pathway and then brought about the elevation of mitochondrial Ca²⁺ via NFATC-targeted MCU. In antler chondrocytes, inactivation of YAP disrupted the mitochondrial morphology, diminished the ATP content and lowered the mitochondrial membrane potential, but these effects were neutralized by the blockage of MCU. Moreover, inhibition of YAP promoted the leakage of mtROS from dysfunctional mitochondria into the cytosol through opening the mitochondrial permeability transition pore, resulting in intracellular ROS accumulation and lipid peroxidation. Addition of ROS scavenger rescued the defective differentiation of antler chondrocytes and protected chondrocytes against apoptosis under the context of YAP inactivation. Collectively, YAP regulated the hypertrophy and apoptosis of antler chondrocytes through maintaining Ca²⁺ homeostasis and mitochondrial function.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"136 ","pages":"Article 112137"},"PeriodicalIF":3.7,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074357","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":"Elevated P4HB expression in hepatocellular carcinoma and its role in UCA1-mediated malignant progression","authors":"Song Huang ,&nbsp;Yuehong Cai ,&nbsp;Xueqing Zhao ,&nbsp;Xiaohong Du ,&nbsp;Haijun Hu","doi":"10.1016/j.cellsig.2025.112131","DOIUrl":"10.1016/j.cellsig.2025.112131","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, underscoring the urgent need for improved diagnostic and therapeutic strategies. In this study, we investigated the role of Prolyl 4-hydroxylase subunit beta (P4HB) in HCC progression and its potential as a diagnostic biomarker. Single-cell sequencing analysis revealed that P4HB is highly expressed in malignant HCC cell populations. Serum analysis demonstrated that P4HB levels were significantly elevated in HCC patients compared to healthy controls and those with benign liver diseases, with ROC analysis showing a high diagnostic performance, particularly when combined with alpha-fetoprotein (AFP). Functional assays, both in vitro and in vivo, confirmed that P4HB promotes the proliferation, migration, and invasion of HCC cells. Furthermore, we identified a novel interaction between P4HB and the lncRNA UCA1, which enhances glycolysis and malignant behavior in HCC cells. These findings suggest that P4HB is a promising biomarker for HCC diagnosis and a potential therapeutic target, particularly in the context of its interaction with UCA1.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"136 ","pages":"Article 112131"},"PeriodicalIF":3.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058313","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":"Epigenetics of mitochondrial and inflammation in cardiac fibrosis","authors":"Huan-Huan He ,&nbsp;Li-Chan Lin ,&nbsp;Zhen-Yu Liu ,&nbsp;Peng Liu ,&nbsp;Sui Mao ,&nbsp;Wei Cao ,&nbsp;Jian-Yuan Zhao ,&nbsp;Hui Tao","doi":"10.1016/j.cellsig.2025.112133","DOIUrl":"10.1016/j.cellsig.2025.112133","url":null,"abstract":"<div><div>Cardiac fibrosis (CF) is a reactive remodeling process that occurs in response to myocardial injury. It is characterized by the accumulation of extracellular matrix (ECM) proteins in the cardiac interstitium, resulting in thickening of the myocardial wall and impaired cardiac function. This ultimately leads to heart failure. Various heart injuries, including ischemia and infection, can trigger inflammatory reactions in the heart, leading to chronic inflammation and progressive structural damage, which contribute to CF. Inflammation and fibrosis are closely intertwined and play crucial roles in the development of heart failure. The myocardium, being a highly oxidized tissue, requires high energy for continuous blood pumping. Mitochondria, the energy centers of cells, are essential for maintaining optimal heart performance. They also play a significant role in promoting inflammation and responding to pathogenic infections. In this article, we review the pathological mechanisms of mitochondrial-controlled inflammatory response in CF and explore the inflammatory regulatory effects and molecular mechanisms of CF from an epigenetic perspective. We provide a brief introduction to promising molecular regulatory factors that target epigenetics, which may serve as potential mitochondrial targets for CF. Finally, we discuss the potential application of these findings in improving the treatment and prevention of CF.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"136 ","pages":"Article 112133"},"PeriodicalIF":3.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063648","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":"NCAPD2 stimulates glycolysis and esophageal cancer metastasis through Wnt5A-dependent Notch activation","authors":"Qian Xu ,&nbsp;Sheng Yang","doi":"10.1016/j.cellsig.2025.112120","DOIUrl":"10.1016/j.cellsig.2025.112120","url":null,"abstract":"<div><h3>Background</h3><div>Although non-SMC condensin I complex subunit D2 (NCAPD2) is a significant player in multiple tumors, its role in esophageal cancer (EC) remains poorly defined. This study aimed to investigate the molecular mechanisms by which NCAPD2 influenced EC metastasis.</div></div><div><h3>Methods</h3><div>The mechanism of NCAPD2 in EC cells was analyzed through transcriptome sequencing. The extracellular acidification rate (ECAR), oxygen consumption rate (OCR), lactate production, and glucose consumption were measured using assay kits to evaluate the level of glycolytic metabolism. Western blot was used to validate the expression of critical glycolytic enzymes, EMT markers, and Notch signaling components. Cell migration and invasion were assessed through scratch and Transwell assays. In vivo experiments included the establishment of subcutaneous tumors in BALB/c nude mice to monitor tumor growth and assess invasiveness via H&amp;E staining. The expression of NCAPD2, Wnt5A, Notch pathway, and EMT-related proteins was detected by immunohistochemistry.</div></div><div><h3>Results</h3><div>NCAPD2 overexpression in EC cells enhanced their ability to migrate and invade by promoting glycolysis—a process tightly linked to the activation of Wnt5A. Specifically, NCAPD2 drove up Wnt5A levels, which in turn boosted glycolytic flux. This metabolic shift relied on the activation of the Notch pathway by Wnt5A, ultimately fueling the metastatic potential of EC.</div></div><div><h3>Conclusion</h3><div>NCAPD2 enhanced the proliferation and metastasis of EC cells by promoting glycolysis through Wnt5A-mediated activation of the Notch pathway. This finding not only revealed the critical role of the NCAPD2/Wnt5A axis in EC but also provided a potential therapeutic target for EC treatment.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"136 ","pages":"Article 112120"},"PeriodicalIF":3.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063666","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}