Cellular signalling最新文献

{"title":"Biliverdin alleviates cerebral ischemia-reperfusion injury by regulating the P4hb/MAPK/mTOR pathway to inhibit autophagy","authors":"Huan Jiang ,&nbsp;Wenya Bai ,&nbsp;Yuan Yang ,&nbsp;Guilin Zhou ,&nbsp;Junjie Li ,&nbsp;Xuelian Li ,&nbsp;Xiaohong Wan ,&nbsp;Jianlin Shao","doi":"10.1016/j.cellsig.2025.111815","DOIUrl":"10.1016/j.cellsig.2025.111815","url":null,"abstract":"<div><h3>Background</h3><div>Biliverdin (BV) exhibits anti-inflammatory and antioxidative effects. Autophagy activation is crucial in the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). This study aimed to investigate whether BV could ameliorate CIRI by regulating autophagy.</div></div><div><h3>Methods</h3><div>A middle cerebral artery occlusion-reperfusion (MCAO/R) model in Sprague-Dawley (SD) rats and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in PC12 cells were employed to explore the neuroprotective effects of BV and its underlying mechanisms. In these rats, once BV was administered post-MCAO/R, its treatment efficacy and underlying mechanisms were evaluated through behavioral, morphological, and molecular analyses. Alternatively, for PC12 cells, following successful OGD/R modeling, BV, autophagy activator rapamycin, prolyl 4-hydroxylase beta (P4hb) knockdown or overexpression, and the specific inhibitors of three classic autophagy pathways were applied. Cell viability (using CCK8 assay), Calcein/PI staining, autophagosome staining (using MDC assay), reverse transcription quantitative polymerase chain reaction, and western blot were subsequently carried out to investigate the mechanisms by which BV ameliorates CIRI.</div></div><div><h3>Results</h3><div>BV alleviated CIRI by inhibiting autophagy. Further investigation suggested that BV downregulated P4hb expression. In vitro experiments showed that P4hb knockdown reduced autophagy in post-CIRI cells, while its overexpression reversed the effects of BV. Rescue experiments indicated that MAPK pathway inhibitors counteracted the effects of P4hb overexpression on autophagy post-CIRI.</div></div><div><h3>Conclusion</h3><div>BV improves CIRI by regulating the P4hb/MAPK/mTOR signaling pathway to inhibit autophagy, offering a novel therapeutic strategy for ischemic stroke.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111815"},"PeriodicalIF":4.4,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856008","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":"MINT3 promotes STING activation and facilitates antiviral immune responses","authors":"Yue Fu ,&nbsp;Caiwei Wang ,&nbsp;Wenyue Sun ,&nbsp;Hongyi Kong ,&nbsp;Wenbo Liang ,&nbsp;Tongrui Shi ,&nbsp;Qizhao Li ,&nbsp;Mutian Jia ,&nbsp;Wei Zhao ,&nbsp;Hui Song","doi":"10.1016/j.cellsig.2025.111825","DOIUrl":"10.1016/j.cellsig.2025.111825","url":null,"abstract":"<div><div>Stimulator-of-interferon genes (STING) translocation is the rate-limiting step in the cGAS-STING signaling which detects cytosolic DNA and produces type I interferons. However, the mechanism by which this process is modulated remains to be further clarified. In the present study, we identified munc18–1-interacting protein 3 (MINT3) as a positive regulator of STING signaling. MINT3 promotes type I interferons production induced by herpes simplex virus-1 (HSV-1) infection and ISD or cGAMP stimulation in mouse peritoneal macrophages. Deficiency of <em>Mint3</em> greatly inhibited STING and IRF3 activation in macrophages. <em>Mint3</em> knockdown also attenuated STING and IRF3 activation in macrophages, human THP-1 cells, and RAW264.7 cells. Mechanistically, MINT3 interacted with STING, selectively enhanced its K63-linked polyubiquitination and facilitated STING translocation to the Golgi, resulting in the enhancement of the STING and TBK1 interaction. Furthermore, MINT3 also facilitated HSV-1-induced innate antiviral immune responses and impaired HSV-1 replication <em>in vitro</em> and <em>in vivo</em>. Interestingly, we showed that the expression of MINT3 was dramatically elevated during HSV-1 infection, and ISD stimulation in macrophages. Thus, we have revealed a feedback mechanism for the regulation of the cGAS-STING pathway, providing a promising therapeutic target for the treatment of disorders triggered by aberrant STING activity.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111825"},"PeriodicalIF":4.4,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874608","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":"Glioblastoma cells secrete ICAM1 via FASN signaling to promote glioma-associated macrophage infiltration","authors":"Wenxin Zhang ,&nbsp;Jialin Wang ,&nbsp;Jiayu Ji ,&nbsp;Peiwen Wang ,&nbsp;Guiqiang Yuan ,&nbsp;Sheng Fang ,&nbsp;Fusheng Liu ,&nbsp;Guishan Jin ,&nbsp;Junwen Zhang","doi":"10.1016/j.cellsig.2025.111823","DOIUrl":"10.1016/j.cellsig.2025.111823","url":null,"abstract":"<div><div>Glioma-associated macrophages (GAMs) constitute the most abundant subset of immune cells in the glioblastoma (GBM) microenvironment, but the underlying mechanism of intense infiltration needs to be elucidated. In this study, we found that GBM cells secrete ICAM1 via FASN signaling to promote GAM infiltration. FASN expression is correlated with GAM density in GBM patients. In vitro experiments revealed that FASN regulates the type-I interferon pathway, particularly STAT1 expression. Moreover, disrupting FASN-STAT1 signaling through the overexpression or inhibition of FASN or STAT1 in GBM cells strongly influences microglial recruitment. Additionally, ICAM1 acts as a direct transcriptional candidate of FASN-STAT1 and a paracrine soluble factor, recruiting microglia to GBM tumors. This study revealed crosstalk between GBM cells and GAMs through FASN-STAT1-ICAM1 signaling to promote microglial infiltration, suggesting potential strategies for treating GBM patients.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111823"},"PeriodicalIF":4.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850075","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":"Decoding the role of nucleic acid binding protein 2 in lipid dysregulation and hepatocellular carcinoma progression through LKB1-mediated mitochondrial dysfunction","authors":"Chengchen Dai ,&nbsp;Yun Tong ,&nbsp;Nan Bai ,&nbsp;Nuo Xu ,&nbsp;Xuying Zhao ,&nbsp;Lihua Zhou ,&nbsp;Zhangzhi Tang ,&nbsp;Mingyu Liu ,&nbsp;Banglong Xu ,&nbsp;Xiaoquan Liu ,&nbsp;Yinqi Chen ,&nbsp;Zhaoyi Lin ,&nbsp;Jinlong Li ,&nbsp;Saiyan Bian ,&nbsp;Wenjie Zheng","doi":"10.1016/j.cellsig.2025.111820","DOIUrl":"10.1016/j.cellsig.2025.111820","url":null,"abstract":"<div><div>Nucleic Acid Binding Protein 2 (NABP2), a crucial regulator in the single-stranded DNA-binding protein family, has been linked to the progression of hepatocellular carcinoma (HCC) and poor prognosis. However, the precise mechanisms by which NABP2 regulates HCC development, especially through metabolic pathways, remain unclear. In this study, we evaluated NABP2 expression in clinical HCC samples and analyzed its correlation with patient survival outcomes. Functional assays, including cell proliferation, migration, and lipid metabolism analyses, were performed in vitro and in vivo to investigate the role of NABP2 in tumorigenesis. Additionally, we examined the molecular interactions of NABP2 with the E3 ubiquitin ligase STUB1 and its impact on the LKB1/AMPK signaling pathway. Our results revealed that NABP2 was overexpressed in HCC tissues and associated with worse survival outcomes. NABP2 promoted tumor cell proliferation, migration, and disrupted lipid metabolism. Mechanistically, NABP2 regulated the proteostasis of liver kinase B1 (LKB1) by recruiting STUB1, leading to the inhibition of the LKB1/AMPK signaling axis and mitochondrial dysfunction. In conclusion, our findings suggest that NABP2 may serve as both a biomarker and a potential therapeutic target for HCC, offering novel insights into its role in metabolic reprogramming and tumor progression.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111820"},"PeriodicalIF":4.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843635","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":"PKA restricts ERK signaling in learning and memory Kenyon cell neurons","authors":"James C. Sears ,&nbsp;Kendal Broadie","doi":"10.1016/j.cellsig.2025.111818","DOIUrl":"10.1016/j.cellsig.2025.111818","url":null,"abstract":"<div><div>Protein Kinase A (PKA) and Extracellular Signal-Regulated Kinase (ERK) have core roles in learning and memory. Here, we investigate kinase-kinase signaling interactions in the <em>Drosophila</em> brain Kenyon cell learning/memory circuit using separation of phases-based activity reporter of kinase (SPARK) biosensors to image circuit-localized functions in vivo. We find that constitutively active Rapidly Accelerated Fibrosarcoma (RAF^gof) enhances ERK signaling only in Kenyon cell domains with low baseline PKA signaling, and that transgenic inhibition of PKA function elevates ERK signaling. Conversely, loss of ERK has no impact on PKA signaling, whereas RAF^gof expands PKA signaling. Importantly, transgenic PKA inhibition together with RAF^gof synergistically elevates ERK signaling. These findings indicate a negative PKA-ERK pathway interaction within learning/memory Kenyon cells. We find that potentiating circuit activity using an exogenous NaChBac ion channel elevates PKA signaling in circuit domains with low baseline PKA function, and uniformly strongly increases ERK signaling. Similarly, thermogenetic stimulation of circuit activity with a temperature-sensitive TRPA1 channel increases PKA signaling in circuit domains of low baseline PKA, and elevates ERK signaling. Importantly, potentiating circuit activity (NaChBac) while also inhibiting PKA function synergistically elevates ERK signaling. Likewise, conditional induction of circuit activity (TRPA1) together with PKA inhibition increases activity-dependent ERK signaling. Finally, a mechanically-induced seizure model (bang-sensitive <em>sesB</em> mutant) elevates PKA signaling, while simultaneous transgenic PKA inhibition in this model acts to synergistically increase ERK signaling. Taken together, we conclude PKA limits ERK signaling in Kenyon cells within the learning and memory circuit, with PKA function acting to restrict activity-dependent ERK signaling.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111818"},"PeriodicalIF":4.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843516","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":"MTHFD2: A metabolic checkpoint altering trophoblast invasion and migration by remodeling folate-nucleotide metabolism in recurrent spontaneous abortion","authors":"Qingxin Xu ,&nbsp;Yicheng Zhou ,&nbsp;Meijuan Wu ,&nbsp;Shengnan Wu ,&nbsp;Jing Yu ,&nbsp;Yao Xu ,&nbsp;Zhiyun Wei ,&nbsp;Liping Jin","doi":"10.1016/j.cellsig.2025.111808","DOIUrl":"10.1016/j.cellsig.2025.111808","url":null,"abstract":"<div><div>Recurrent spontaneous abortion (RSA) affects female reproduction worldwide, yet its pathological mechanisms are still unclear. It has been reported that cellular metabolism reprogramming is a critical step for trophoblasts during embryo implantation. Herein, MTHFD2 was recognized as a key metabolic checkpoint attributed to RSA occurrence. This work figured out that the expression level of MTHFD2 was significantly inhibited in villus tissues from RSA patients, suggesting the potential role of MTHFD2 in RSA occurrence. Moreover, MTHFD2 knockdown impaired cellular folate-nucleotide metabolism, induced the accumulation of AICAR, and thereby impairing the EMT process to inhibit the invasion and migration of trophoblasts Besides, the AICAR accumulation further activated the downstream AMPK which deactivated the JAK/STAT/Slug pathway and ultimately deactivated the EMT process. Using a mouse model, MTHFD2 inhibition was observed to induce embryo implantation failure in vivo. Our results highlighted MTHFD2 as a metabolic checkpoint that remodeled folate-nucleotide metabolism to regulate the EMT process and ultimately altered the migration and invasion of trophoblasts in RSA occurrence. Our findings suggested that MTHFD2 was a promising therapeutic target in recurrent spontaneous abortion treatment.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111808"},"PeriodicalIF":4.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856009","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":"PRIM1 enhances colorectal cancer liver metastasis via promoting neutrophil recruitment and formation of neutrophil extracellular trap","authors":"Ju Wu ,&nbsp;Jianhui Song ,&nbsp;Yuzhuang Ge ,&nbsp;Shuangshuang Hou ,&nbsp;Yaoyuan Chang ,&nbsp;Xi Chen ,&nbsp;Zhequn Nie ,&nbsp;Lianyi Guo ,&nbsp;Jiajun Yin","doi":"10.1016/j.cellsig.2025.111822","DOIUrl":"10.1016/j.cellsig.2025.111822","url":null,"abstract":"<div><div>Despite advances in treatment, liver metastasis remains the predominant pattern of distant spread for colorectal cancer (CRC) and a major cause of cancer-related mortality. DNA Primase Subunit 1 (PRIM1) has been reported to play important roles in cancer progression. This study investigated the role of PRIM1 in CRC liver metastasis, focusing on its influence on neutrophil recruitment and the formation of neutrophil extracellular traps (NETs). In this study, PRIM1 was upregulated in liver metastasis tumor tissues. CCK-8 and Transwell assays showed that the proliferation, migration and invasion of CRC cells were promoted with the ablation of PRIM1 and inhibited with PRIM1 overexpression. For in vivo investigation, we observed that PRIM1 ablation reduced the number and size of metastasis nodules of MC38 cells. Importantly, PRIM1 depletion obviously reduced the percentage of Ly6G+ neutrophils in liver. In contrast, overexpression of PRIM1 reversed these effects. Besides, depletion of neutrophils by anti-Ly6G antibody in mice notably attenuated liver metastasis burden induced by the upregulation of PRIM1. Western blot and immunohistochemistry assays revealed that three chemokines CXCL8, C-GSF and CXCL2 were confirmed to be upregulated with PRIM1 overexpression. Furthermore, PRIM1 overexpression reduced the formation of NETs. These results suggested that PRIM1 could facilitate the liver metastasis of CRC via recruiting neutrophils and NET formation. In conclusion, our novel findings highlighted the important role of PRIM1 in neutrophil recruitment and CRC metastasis and provided new perspectives and potential targets for future research and treatment for CRC.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111822"},"PeriodicalIF":4.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856033","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":"Circ847 upregulation via CAFs suppresses salivary adenoid cystic carcinoma progression through VIM-EMT","authors":"Yancan Liang ,&nbsp;Yuwei Zhou ,&nbsp;Tianshu Xu ,&nbsp;Yan Wang ,&nbsp;Xiaoxian Xu ,&nbsp;Rui Chen ,&nbsp;Qiming Jiang ,&nbsp;Nan Lu ,&nbsp;Luodan Zhao ,&nbsp;Zhiquan Huang ,&nbsp;Zixian Huang","doi":"10.1016/j.cellsig.2025.111806","DOIUrl":"10.1016/j.cellsig.2025.111806","url":null,"abstract":"<div><div>Salivary adenoid cystic carcinoma (SACC) is prone to metastasis, which strongly affects its prognosis. Cancer-associated fibroblasts (CAFs) play important roles in SACC metastasis. The purpose of this study was to identify and explore the key regulatory mechanisms of the altered expression of circRNAs in SACC CAFs.</div><div>In this study, we found that circRNA-847 (circ847) expression was inhibited by pretreatment with SACC CAFs. Cell function experiments confirmed that the downregulation of circ847 promoted the proliferation and metastasis of SACC cells and that overexpression of circ847 induced the opposite effects. Mechanistically, circ847 can bind to vimentin and regulate its stability, thereby regulating epithelial–mesenchymal transition (EMT)-related signaling. Histological staining of SACC patient specimens also confirmed that the expression of circ847 was negatively correlated with SACC lymph node and lung metastasis. As a proof of concept, we successfully inhibited SACC progression and metastasis in sciatic nerve invasion models and lung metastasis models of SACC by treating the mice with nanoparticle-encapsulated circ847 plasmids to induce circ847 overexpression.</div><div>This study demonstrated that circ847 expression is inhibited by CAFs. Restoring the expression of circ847 can effectively inhibit the progression of SACC, providing new research ideas for the study of effective prevention and treatment strategies for SACC and the prediction of SACC distant metastasis risk and prognosis.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111806"},"PeriodicalIF":4.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852204","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":"USP7 promotes the malignant progression of osteosarcoma through the KPNA2/PKLR axis","authors":"Mao Wang,&nbsp;Yuxia Shi,&nbsp;Zhizhong Liang,&nbsp;Fan Yang","doi":"10.1016/j.cellsig.2025.111819","DOIUrl":"10.1016/j.cellsig.2025.111819","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma, a common primary bone malignancy, poses significant challenges in clinical treatment due to its high metastatic potential and resistance to chemotherapy. The karyopherin subunit alpha 2 (KPNA2) is a member of the karyopherin family and has been implicated in the regulation of various cellular processes. However, the role of KPNA2 in osteosarcoma development and progression remains unclear.</div></div><div><h3>Methods</h3><div>The expression levels of KPNA2 and pyruvate kinase L/R (PKLR) mRNA were assessed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Protein expression of KPNA2, ubiquitin-specific peptidase 7 (USP7), and PKLR was determined <em>via</em> western blotting. Cell viability, proliferation, apoptosis, invasion, and migration were evaluated using CCK-8, EdU, flow cytometry, transwell invasion, and wound-healing assays, respectively. Glucose consumption and lactate production were measured using colorimetric assays. The interaction between USP7 and KPNA2 was identified through co-immunoprecipitation (Co-IP) and immunofluorescence co-localization assays. <em>In vivo</em> experiments were conducted to validate the effects of KPNA2 silencing and PKLR overexpression on osteosarcoma cell growth. The positive expression rates of Ki67 and PKLR were assessed using immunohistochemistry (IHC) assays.</div></div><div><h3>Results</h3><div>KPNA2 expression was upregulated in osteosarcoma tissues and cells. Silencing KPNA2 suppressed osteosarcoma cell proliferation, invasion, migration, and glycolysis, while inducing apoptosis. USP7 stabilized KPNA2 through its deubiquitinating activity, and USP7 silencing inhibited the malignant phenotypes of osteosarcoma cells by regulating KPNA2. Additionally, KPNA2 upregulated PKLR expression, and overexpression of PKLR mitigated the effects of KPNA2 silencing on the malignant progression of osteosarcoma cells both <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>The deubiquitination of KPNA2 by USP7 promoted the malignant progression of osteosarcoma by increasing PKLR expression. This study highlights the clinical significance of targeting the KPNA2-USP7-PKLR axis as a potential therapeutic strategy for the treatment of osteosarcoma.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111819"},"PeriodicalIF":4.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860469","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":"TDH-11 inhibits the proliferation and colonization of colorectal cancer by reducing the activity of HDAC","authors":"Rulei Zhong ,&nbsp;Chenyang Qiu ,&nbsp;Shixin Chan ,&nbsp;Yiming Wang ,&nbsp;Kaige Liu ,&nbsp;Yihui Xia ,&nbsp;Huabing Zhang ,&nbsp;Bingbing Zou","doi":"10.1016/j.cellsig.2025.111817","DOIUrl":"10.1016/j.cellsig.2025.111817","url":null,"abstract":"<div><div>Histone deacetylase inhibitors (HDACIs) have demonstrated significant efficacy and minimal toxic side effects in certain hematological tumors. Nevertheless, their utilization in the therapy of solid tumors, including colorectal cancer (CRC), is constrained by the occurrence of adverse effects such as myelosuppression and cardiotoxicity. Therefore, the development of more efficient and safer HDACIs is crucial for managing CRC. Here, the effects of TDH-11 (a novel HDAC inhibitor) and the underlying molecular mechanisms that inhibits the deveolpment and progression of CRC cells were investigated using in vitro and in vivo experiments<em>.</em> The results indicated that TDH-11 inhibited CRC tumorigenic behavior while also promoted apoptosis and cell cycle arrest. In vivo, TDH-11 markedly inhibited tumor progression and reduces tumor colonization without causing substantial damage to key organs, such as the kidneys, heart, lungs, spleen, and liver. Results of RNA sequencing and western blot suggested that TDH-11 exerted its antitumor effects through modulation of the p53 signaling pathway and its downstream pathways involved in apoptosis and cell cycle regulation. In summary, TDH-11 exhibited significant potential in suppressing the growth and colonization of CRC, as determined in both cellular and animal models. These results provided novel insights into CRC-associated pathways and suggest promising prospects for managing advanced and metastatic CRC.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111817"},"PeriodicalIF":4.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874607","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}