Cellular signalling最新文献_第2页

Aerobic exercise alleviates chronic allergic airway inflammation by regulating the circMETTL9/EIF4A3/IGFBP3 axis 有氧运动通过调节circmetl9 /EIF4A3/IGFBP3轴减轻慢性变应性气道炎症

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-05-26 DOI: 10.1016/j.cellsig.2025.111889

Haixia Wang , Yuanmin Jia , Bin Ma , Ting Gao , Hui Wei , Danyang Li , Junlian Gu , Ou Chen , Shouwei Yue

{"title":"Aerobic exercise alleviates chronic allergic airway inflammation by regulating the circMETTL9/EIF4A3/IGFBP3 axis","authors":"Haixia Wang , Yuanmin Jia , Bin Ma , Ting Gao , Hui Wei , Danyang Li , Junlian Gu , Ou Chen , Shouwei Yue","doi":"10.1016/j.cellsig.2025.111889","DOIUrl":"10.1016/j.cellsig.2025.111889","url":null,"abstract":"<div><div>Aerobic exercise has been recommended as a non-pharmacological treatment for asthma. Previous studies have shown that circMETTL9 regulates cellular inflammation, apoptosis, and oxidative stress levels. However, whether aerobic exercise can modulate the expression of circMETTL9 to alleviate chronic allergic airway inflammation remains unclear. In this study, we established a mouse model of chronic allergic lung inflammation with aerobic exercise intervention to assess its effects. Our results demonstrate that aerobic exercise exerts anti-inflammatory, anti-proliferative, anti-apoptotic, and anti-oxidative stress effects by regulating the circMETTL9/EIF4A3/IGFBP3 axis. Mechanistically, we found that circMETTL9 binding to EIF4A3 does not affect EIF4A3 expression. However, EIF4A3 positively regulates both the protein and mRNA levels of IGFBP3. Specifically, circMETTL9 binds to EIF4A3 to inhibit IGFBP3 transcription and translation. This study identifies a novel potential target and research direction for treating chronic allergic lung inflammation.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"134 ","pages":"Article 111889"},"PeriodicalIF":4.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144170050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A brief overview of the E3 ubiquitin ligase: TRIM7 E3泛素连接酶TRIM7简介

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-05-24 DOI: 10.1016/j.cellsig.2025.111886

Jun-Jie Fan , Can Hu , Min Hu , Wen-Sheng Dong , Kang Li , Yun-Jia Ye , Xin Zhang

{"title":"A brief overview of the E3 ubiquitin ligase: TRIM7","authors":"Jun-Jie Fan , Can Hu , Min Hu , Wen-Sheng Dong , Kang Li , Yun-Jia Ye , Xin Zhang","doi":"10.1016/j.cellsig.2025.111886","DOIUrl":"10.1016/j.cellsig.2025.111886","url":null,"abstract":"<div><div>TRIM7, a member of the E3 ubiquitin ligase family, has garnered significant attentions in different research fields since its discovery. This enzyme plays indispensable roles in various pathophysiological processes through ubiquitination-mediated degradation of diverse protein substrates. This review systematically summarizes the current knowledge on the protein structure and biological functions of TRIM7. Structurally, TRIM7 features a conserved RBCC motif (RING, B-box, and coiled-coil domains) coupled with a variable C-terminal region that dictates the substrate specificity. In infectious contexts, TRIM7 is required for the pathogen-specific regulation, and exerts paradoxical effects by either promoting host defense or facilitating viral pathogenesis depending on pathogen type. Within oncology, TRIM7 manifests tumor-suppressive properties through regulating metastasis, apoptosis, and tumor immunology. In addition, it might serve as a reliable biomarker for monitoring the progression of idiopathic pulmonary fibrosis and also inhibits the progression of atherosclerosis. In summary, TRIM7 plays critical roles in different pathophysiological processes, and it might be a predictive and therapeutic target in certain human diseases.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"134 ","pages":"Article 111886"},"PeriodicalIF":4.4,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Primary cilium restricts TGF-β/SMAD signaling induced RIBEs in the co-culture model. 在共培养模型中，初级纤毛限制TGF-β/SMAD信号诱导的RIBEs。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-05-22 DOI: 10.1016/j.cellsig.2025.111891

Pei Qu , Yuan Wang , Zhi'ang Shao , Dong Lu , Taisei Mamiya , Wei Wang , Jinpeng He , Yanan Zhang , Wenjun Wei , Junrui Hua , Dan Xu , Teruaki Konishi , Jufang Wang , Nan Ding

{"title":"Primary cilium restricts TGF-β/SMAD signaling induced RIBEs in the co-culture model.","authors":"Pei Qu , Yuan Wang , Zhi'ang Shao , Dong Lu , Taisei Mamiya , Wei Wang , Jinpeng He , Yanan Zhang , Wenjun Wei , Junrui Hua , Dan Xu , Teruaki Konishi , Jufang Wang , Nan Ding","doi":"10.1016/j.cellsig.2025.111891","DOIUrl":"10.1016/j.cellsig.2025.111891","url":null,"abstract":"<div><div>Transforming growth factor β (TGF-β) is the predominant cytokine responding to ionizing radiation and participates in radiation induced bystander effects (RIBEs). Primary cilia (PC) coordinates with multiple signaling pathways, exhibit specialized functions in TGF-β signal transduction. Our previous studies using a medium transfer model revealed that PC modulates RIBEs by restricting TGF-β signaling. To further investigate PC's mechanistic role in RIBEs, proton microbeam radiation (MR) and partial radiation (PR) were used to arrange the co-culture bystander system. Key methodologies included siRNA-mediated PC formation modulation, inhibition of DNA damage response kinases ataxia telangiectasia-mutated gene (ATM), Ataxia telangiectasia and Rad3-related protein (ATR) or DNA-dependent protein kinase (DNApk), and quantitative analysis of γH2AX foci, cell proliferation, and reactive oxygen/nitrogen species (ROS/NO). The results showed that, firstly, PC inhibition in both PR and MR models significantly increased γH2AX foci formation and protein levels within 12 h while suppressing cell proliferation, which were reversed by TGF-β signaling inhibition. Secondly, although inhibition of ATM, ATR, or DNApk reduced γH2AX foci but resulted in decrease of proliferation rate. Scavenging ROS/NO similarly attenuated DNA damage but enhanced cell survival. Third, SMAD2/3 complex inhibition in PC-deficient bystander cells downregulated ATM/ATR expression and reduced intracellular NO/ROS levels. These results demonstrate that TGF-β1 drives RIBEs-associated DNA damage through canonical p-SMAD2/3 signaling, which amplifies ROS/NO production and hyperactivates ATM, ATR or DNApk. Crucially, PC acts as a regulatory role in DNA damages of RIBEs progression.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"134 ","pages":"Article 111891"},"PeriodicalIF":4.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

KIF18B drives the malignant progression of gliomas by activating the Notch pathway KIF18B通过激活Notch通路驱动胶质瘤的恶性进展

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-05-21 DOI: 10.1016/j.cellsig.2025.111888

Liang Zhang , Fei Li , Lingxue Zhang , Yuyan Zhou , Yusheng Liu , Jing Liu , Yilun Cheng , Jianjun Shu , Haikang Zhao , Yao Wei

{"title":"KIF18B drives the malignant progression of gliomas by activating the Notch pathway","authors":"Liang Zhang , Fei Li , Lingxue Zhang , Yuyan Zhou , Yusheng Liu , Jing Liu , Yilun Cheng , Jianjun Shu , Haikang Zhao , Yao Wei","doi":"10.1016/j.cellsig.2025.111888","DOIUrl":"10.1016/j.cellsig.2025.111888","url":null,"abstract":"<div><div>Kinesin family member 18B (KIF18B) is expressed differently in multiple malignancies and contributes to tumorigenesis. However, the relevance of KIF18B in glioma remains undetermined. This work evaluated the level and clinical significance of KIF18B in glioma. The upregulation of KIF18B was frequently detected in glioma specimens, which was related to clinicopathological features and therapeutic outcomes. A decrease in KIF18B expression in glioma cells was found to suppress malignant proliferation and metastasis, while simultaneously enhancing the cells' sensitivity to chemotherapeutic agents. Bioinformatics analysis demonstrated a significant correlation between KIF18B and the Notch signaling pathway in glioma cells. Further experimental validation confirmed that silencing KIF18B effectively inhibited the activation of the Notch signaling pathway. Reactivation of the Notch signaling pathway remarkably reversed the cancer-suppressing effects of KIF18B knockdown. Moreover, the ability of KIF18B-silenced glioma cells to form xenografts in nude mice was markedly impaired, accompanied by the downregulation of the Notch signaling pathway. This work indicates that KIF18 is crucial for maintaining glioma progression and proposes its potential as a promising therapeutic target for glioma treatment.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"134 ","pages":"Article 111888"},"PeriodicalIF":4.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CALB2 facilitates macrophage M2 polarization to promote the growth and metastasis of pancreatic adenocarcinoma CALB2促进巨噬细胞M2极化，促进胰腺腺癌生长和转移

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-05-21 DOI: 10.1016/j.cellsig.2025.111887

Dongwei Hu , Bo Xu , Guoyu Huang , Xiaowei Hu , Jinjie Li , Zongjing Chen , Wei Liu , Zhengde Wen

{"title":"CALB2 facilitates macrophage M2 polarization to promote the growth and metastasis of pancreatic adenocarcinoma","authors":"Dongwei Hu , Bo Xu , Guoyu Huang , Xiaowei Hu , Jinjie Li , Zongjing Chen , Wei Liu , Zhengde Wen","doi":"10.1016/j.cellsig.2025.111887","DOIUrl":"10.1016/j.cellsig.2025.111887","url":null,"abstract":"<div><div>Tumor-associated macrophages mainly differentiate into M2 phenotypes, which secrete cytokines that reshape the tumor microenvironment and promote tumor progression. This study was to explore the mechanism of CALB2 in M2 polarization and pancreatic adenocarcinoma (PAAD). Clinical tissue samples of PAAD were collected, followed by detection of WTAP, FOSL1, and CALB2 expression. The correlation between WTAP and FOSL1 or between FOSL1 and CALB2 was analyzed. THP1 cells were induced into M0 macrophages, followed by plasmid transfection and induction of M2-type macrophages. After macrophages were co-cultured with PAAD cells, functional experiments were designed to evaluate PAAD cell malignant behaviors. A transplantation tumor model and a liver metastasis model were established to assess tumor growth and metastasis. High expression of WTAP, FOSL1, and CALB2 was found in PAAD tissues and M2-type macrophages. WTAP positively linked with FOSL1, so as FOSL1 and CALB2. Mechanistically, WTAP enhanced m6A modification of FOSL1 to promote its expression, and FOSL1 promoted CALB2 transcription. Knockdown of WTAP, FOSL1, or CALB2 in macrophages inhibited PAAD cell malignant behaviors, which could be reversed by CALB2 upregulation. WTAP knockdown restrained the growth and metastasis of PAAD in nude mice via the FOSL1/CALB2 axis. In conclusion, WTAP increased the m6A level of FOSL1, activated CALB2 transcription, and promoted M2 polarization of macrophages, thereby promoting the growth and metastasis of PAAD.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"134 ","pages":"Article 111887"},"PeriodicalIF":4.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptional regulation of ATOX1 by PRRX2 impacts the progression and cuproptosis of hepatocellular carcinoma PRRX2对ATOX1的转录调控影响肝细胞癌的进展和预后。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-05-18 DOI: 10.1016/j.cellsig.2025.111883

Ling Tang , Bin Xie , Xiankui Cao , Mengze Zhang , Yang Shao

{"title":"Transcriptional regulation of ATOX1 by PRRX2 impacts the progression and cuproptosis of hepatocellular carcinoma","authors":"Ling Tang , Bin Xie , Xiankui Cao , Mengze Zhang , Yang Shao","doi":"10.1016/j.cellsig.2025.111883","DOIUrl":"10.1016/j.cellsig.2025.111883","url":null,"abstract":"<div><div>The copper chaperone antioxidant 1 (ATOX1) has been identified as a potential oncogene in certain types of cancer, and its increased expression is associated with poor prognoses. Nevertheless, its function in hepatocellular carcinoma (HCC) remains largely uninvestigated. An analysis of the UALCAN database and clinical specimens revealed an increase in ATOX1 expression in HCC tissues. <em>In vitro</em> studies showed that ATOX1 knockdown inhibited the proliferation and metastasis of HCC cells, as well as tumor growth in xenograft models. Silencing ATOX1 led to cuproptosis and mitochondrial dysfunction in HCC cells. In contrast, ATOX1 overexpression had opposite effects. The ATOX1 promoter region was predicted to contain several paired related homeobox 2 (PRRX2) binding sites based on the JASPAR database. Further experiments showed that PRRX2 directly bound to ATOX1's promoter and positively regulated its expression. The knockdown of PRRX2 led to the inhibition of cell proliferation, invasion, and EMT, while promoting cuproptosis in HCC cells. However, these effects were found to be partially blocked following the overexpression of ATOX1. The study showed that ATOX1, which is transcriptionally activated by PRRX2, contributes to HCC carcinogenesis by regulating cancer cell malignant behaviors, cuproptosis, and mitochondrial function. The PRRX2/ATOX1 axis could be a potential therapeutic target for HCC.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"134 ","pages":"Article 111883"},"PeriodicalIF":4.4,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sorafenib inhibits multiple sclerosis by regulating T cell differentiation 索拉非尼通过调节T细胞分化抑制多发性硬化症。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-05-17 DOI: 10.1016/j.cellsig.2025.111872

Hanliang Wang , Shuowang Wang , Jin Wang , Yue Fang , Junwei Li , Yingying Shen , Jufeng Guo

引用次数: 0

Morin induces autophagy-dependent ferroptosis in colorectal cancer cells by inhibiting the AURKB-UCHL3 interactions 桑辣素通过抑制AURKB-UCHL3相互作用诱导结直肠癌细胞自噬依赖性铁凋亡。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-05-17 DOI: 10.1016/j.cellsig.2025.111875

Rui Li , Sha He , Fengxia Wang , Shan Liu , Kunyao Xu , Meng Luo

{"title":"Morin induces autophagy-dependent ferroptosis in colorectal cancer cells by inhibiting the AURKB-UCHL3 interactions","authors":"Rui Li , Sha He , Fengxia Wang , Shan Liu , Kunyao Xu , Meng Luo","doi":"10.1016/j.cellsig.2025.111875","DOIUrl":"10.1016/j.cellsig.2025.111875","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) poses a significant threat to human health, and its underlying mechanisms require further exploration. Morin, a natural flavonoid, exhibits anti-CRC activity, but its molecular mechanisms remain unclear. This study aimed to evaluate its anti-CRC effects and elucidate its molecular mechanisms to provide new insights for CRC treatment.</div></div><div><h3>Methods</h3><div>Molecular docking predicted potential binding between morin and AURKB. Experimental validation included qPCR, Western blotting, co-immunoprecipitation, and immunofluorescence. Autophagy-dependent ferroptosis was assessed by measuring mitochondrial superoxide, MDA, GSH, and ROS levels, as well as NCOA4 and FTH1 expression.</div></div><div><h3>Results</h3><div>AURKB is highly expressed in CRC, and stabilized via interaction with the deubiquitinase UCHL3, which activated the PI3K/Akt/mTOR pathway and suppressed autophagy-dependent ferroptosis. This suppression was characterized by reduced mitochondrial superoxide, decreased MDA and ROS levels, elevated GSH, and upregulated FTH1. Morin disrupted the AURKB-UCHL3 interaction, promoted AURKB degradation, reversed ferroptosis inhibition, and suppressed CRC cell proliferation and migration.</div></div><div><h3>Conclusion</h3><div>This study is the first to demonstrate that morin inhibits CRC progression by targeting the AURKB-UCHL3 axis to regulate autophagy-dependent ferroptosis, providing experimental evidence for its therapeutic potential in CRC treatment.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"134 ","pages":"Article 111875"},"PeriodicalIF":4.4,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lactate induces oxidative phosphorylation in osteoblasts via Gpr81–Stat3 signaling 乳酸通过Gpr81-Stat3信号通路诱导成骨细胞氧化磷酸化。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-05-17 DOI: 10.1016/j.cellsig.2025.111877

Xiping Hu , Jin Shen , Ruijian Wang , Chunqing Han , Xian Shi , Jiaxin Hu , Mengqing Zhang , Peiwen Wang , Xian Zhang , Yu Wu

{"title":"Lactate induces oxidative phosphorylation in osteoblasts via Gpr81–Stat3 signaling","authors":"Xiping Hu , Jin Shen , Ruijian Wang , Chunqing Han , Xian Shi , Jiaxin Hu , Mengqing Zhang , Peiwen Wang , Xian Zhang , Yu Wu","doi":"10.1016/j.cellsig.2025.111877","DOIUrl":"10.1016/j.cellsig.2025.111877","url":null,"abstract":"<div><div>Lactate has long been regarded as an end product of glycolysis and a metabolic “waste product” under hypoxic conditions, but recent studies have revealed that lactate plays a central role in energy metabolism reprogramming and intercellular communication. However, it remains unknown whether lactate promotes osteogenic differentiation through metabolic reprogramming. Here, we showed that lactate significantly increased the cellular ATP content, activated succinate dehydrogenase activity, and enhanced oxygen consumption rate in pre-osteoblast MC3T3-E1 cells. Moreover, lactate treatment increased oxidative phosphorylation (OXPHOS) in parathyroid hormone (PTH)-treated MC3T3-E1 cells. Microarray and RNA-sequencing analysis revealed that Stat3 signaling was enriched in MC3T3-E1 cells treated with lactate or co-treated with lactate and PTH. Immunoblotting verification analysis further showed that lactate activated the Jak2–Stat3-Y705 and Akt–Stat3-S727 signaling. Inhibition of Jak2–Stat3-Y705 signaling by AG490 interrupted lactate-induced osteoblast differentiation. Inhibition of Gpr81 by 3-OBA or decrease in Gpr81 expression by Gpr81 siRNA, but not the interruption of MCT1 by AZD3965, led to the inhibition of the Gpr81–Jak2–Stat3-Y705 and Gpr81–Akt–Stat3-S727 signaling, and OXPHOS and cell differentiation of MC3T3-E1 cells were also inhibited. Furthermore, we demonstrated that the Gpr81 subunit G<sub>βγ</sub> plays a central role in lactate–Gpr81 signaling. Lastly, osteoblast Gpr81-deficient mice showed lower bone formation. Thus, these findings propose a novel signaling mechanism by which lactate regulates cell differentiation as well as OXPHOS through the activation of Stat3 signaling by Gpr81.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"133 ","pages":"Article 111877"},"PeriodicalIF":4.4,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TRIM29 promotes liver metastasis via enhancing hepatic colonization by stabilizing FAM83H to regulate keratin network in colorectal cancer TRIM29通过稳定FAM83H调节结直肠癌角蛋白网络，增强肝脏定植，促进肝转移。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-05-17 DOI: 10.1016/j.cellsig.2025.111871

Yang Fu , Runqing Huang , Ge Qin , Shishi Huang , Jianxia Li , Weixiang Zhan , Fan Bai , Xiaoyu Xie , Jiayu Ling , Yue Cai , Yuqian Xie , You Wu , Runkai Cai , Xinrun Huang , Yanhong Deng

{"title":"TRIM29 promotes liver metastasis via enhancing hepatic colonization by stabilizing FAM83H to regulate keratin network in colorectal cancer","authors":"Yang Fu , Runqing Huang , Ge Qin , Shishi Huang , Jianxia Li , Weixiang Zhan , Fan Bai , Xiaoyu Xie , Jiayu Ling , Yue Cai , Yuqian Xie , You Wu , Runkai Cai , Xinrun Huang , Yanhong Deng","doi":"10.1016/j.cellsig.2025.111871","DOIUrl":"10.1016/j.cellsig.2025.111871","url":null,"abstract":"<div><div>Liver metastasis is a frequent and severe event of colorectal cancer (CRC), and patients with liver metastases typically exhibit poor prognosis, high recurrence rates and low responsiveness to treatment. However, the precise molecular mechanisms underlying the liver metastasis in CRC remain poorly understood. In this study, through a comprehensive multi-omics approach, we here identify CRC cells with high tripartite motif-containing protein 29 (TRIM29) expression as the critical subset responsible for liver metastasis. Omics-sequencing pathway analyses combined with in vitro functional assays revealed that CRC cells expressing high TRIM29 expression displayed enhanced cell adhesion, proliferation and liver metastasis capabilities. Mechanistically, TRIM29 interacts with FAM83H and stabilizes it by reducing its ubiquitination and degradation, thereby redistributing cellular keratins, which activates the NF-κB pathway and upregulates PLXNB2 expression to enhance cell adhesion and proliferation to promote hepatic colonization and drive CRC liver metastasis. Interestingly, TRIM29 upregulates the expression of PLXNB2 that can bind to the hepatocyte-specific ligand SEMA4G. Importantly, targeting TRIM29-FAM83H-elicited keratin redistribution and PLXNB2 elevation effectively abrogated CRC liver metastasis. Our findings position TRIM29 as a central driver of liver metastasis in CRC and highlight its potential as a therapeutic target for reducing the risk of liver metastasis in patients.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"134 ","pages":"Article 111871"},"PeriodicalIF":4.4,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0