Cell Communication and Signaling最新文献

{"title":"Caffeine mitigates ROS accumulation and attenuates motor neuron degeneration in the wobbler mouse model of amyotrophic lateral sclerosis.","authors":"Aimo Samuel Christian Epplen, Maximilian Rothöft, Sarah Stahlke, Carsten Theiss, Veronika Matschke","doi":"10.1186/s12964-025-02415-5","DOIUrl":"10.1186/s12964-025-02415-5","url":null,"abstract":"<p><strong>Background: </strong>Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by oxidative stress and progressive motor neuron degeneration. This study evaluates the potential neuroprotective effects of caffeine in the Wobbler mouse, an established model of ALS.</p><p><strong>Methods: </strong>Wobbler mice received caffeine supplementation (60 mg/kg/day) via drinking water, and key parameters, including muscle strength, NAD metabolism, oxidative stress, and motor neuron morphology, were assessed at critical disease stages.</p><p><strong>Results: </strong>Caffeine delayed motor performance decline, as observed in grip strength tests during the early symptomatic phase. Histological analyses revealed that significantly fewer motor neurons were lost in caffeine-treated mice at p41, despite no changes in soma morphology. Biochemical assays demonstrated that caffeine significantly reduced ROS levels and restored NAD levels to wildtype-like values, although NMNAT2 protein expression remained unaffected. The data suggest that caffeine mitigates oxidative stress through alternative pathways, potentially involving enhanced mitochondrial function and antioxidative defenses.</p><p><strong>Conclusions: </strong>These findings highlight the potential of caffeine as a protective agent for delaying motor neuron degeneration in ALS. Future studies should explore optimal dosing strategies, combinatorial treatment approaches, and the underlying molecular mechanisms, to enable translation of these findings to human ALS patients.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"394"},"PeriodicalIF":8.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034686","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":"Targeting mitochondrial proteases CLPP and LONP1 via disruption of mitochondrial redox homeostasis induces proteotoxic stress and suppresses tumor progression.","authors":"Shivani R Nandha, R S Patwardhan, Deepak Sharma, Santosh K Sandur, Rahul Checker","doi":"10.1186/s12964-025-02127-w","DOIUrl":"10.1186/s12964-025-02127-w","url":null,"abstract":"<p><strong>Background: </strong>Cancer cells, which rely heavily on mitochondria for their energy demands and oncometabolites, have a high mitochondrial load, often associated with an aggressive, invasive, and metastatic phenotype. Mitochondrial ROS (mtROS), which play a causal role in cancer, represent the Achilles' heel of cancer since excessive mtROS causes protein misfolding/aggregation, resulting in cell death via proteotoxic stress. Furthermore, the detailed underlying mechanism(s) of mitochondrial oxidative stress-induced cell death remain obscure.</p><p><strong>Methods: </strong>Cell growth was estimated by MTT assay, clonogenic assay, live-cell imaging and flow cytometry. Intracellular ROS, mtROS, glutathione and antioxidant levels were studied by spectrophotometry. RNAseq and Western blotting were performed to elucidate the underlying mechanism(s). In vivo efficacy was evaluated using a syngeneic mouse model.</p><p><strong>Results: </strong>We employed a mitochondria-targeted agent to disrupt the mitochondrial redox balance. Among tumors of different origins, such as lung, breast, prostate, bone, skin, cervical and liver, triple-negative breast cancer (TNBC) exhibited the highest sensitivity to mitochondrial oxidative stress. Compared with the parent compound, mitochondria-targeted agent showed 39-fold more effectiveness in killing TNBCs. We observed a possible correlation between the mitochondrial load in different cancer cell lines and their sensitivity to mitochondrial oxidative stress. Transcriptomic analysis revealed an enrichment of biological response to unfolded and/or misfolded proteins, which are regulated by two key proteases, Lon peptidase 1 (LONP1) and Caseinolytic protease P (CLPP), that control mitochondrial proteostasis. Bioinformatics analyses revealed enhanced expression and a strong positive correlation between these proteases in breast cancer patients, with highest expression observed in TNBC. Additionally, an early relapse was observed in breast cancer patients over-expressing both LONP1 and CLPP. Mitochondrial oxidative stress triggered a decrease in the native functional forms and an increase in the aggregated forms of LONP1 and CLPP, thereby disrupting mitochondrial proteostasis. Interestingly, no such changes were observed in normal cells. Mechanistically, excess mtROS induced proteotoxic stress and mitochondrial dysfunction, culminating in growth inhibition both in vitro and in vivo.</p><p><strong>Conclusion: </strong>Our studies, for the first time, show that the mitochondrial load and induction of mtROS for concomitant inhibition of LONP1 and CLPP to induce proteotoxic stress, could be novel therapeutic targets for cancer.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"393"},"PeriodicalIF":8.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994540","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":"ATE1 promotes breast cancer progression via arginylation-dependent regulation of MAPK-MYC signaling.","authors":"Laxman Nawale, Shinyeong Ju, Jung Gi Kim, Nak Kyun Soung, Bo Yeon Kim, Cheolju Lee, Hyunjoo Cha-Molstad","doi":"10.1186/s12964-025-02376-9","DOIUrl":"10.1186/s12964-025-02376-9","url":null,"abstract":"<p><strong>Background: </strong>Arginyl-tRNA-protein transferase (ATE1) catalyzes N-terminal arginylation, a regulatory protein modification implicated in various cellular processes, including proliferation, apoptosis, and migration. Although ATE1 has context-dependent roles in cancer, its specific function in breast cancer remains unclear. This study investigates the oncogenic role of ATE1 across multiple breast cancer subtypes and its underlying molecular mechanisms.</p><p><strong>Methods: </strong>ATE1 expression in breast cancer was evaluated using TCGA data and immunoblotting across breast cancer cell lines and normal mammary epithelial cells (HMEC). Functional studies using siRNA- and shRNA-mediated knockdown assessed ATE1's role in cell viability, clonogenic growth, migration, and tumorigenesis in vitro and xenograft models. Quantitative proteomics, R-catcher-based N-terminomics, and pathway analyses were employed to identify ATE1-dependent signaling networks, with a focus on MAPK-MYC axis regulation. Flow cytometry and immunoblotting were used to assess cell cycle progression, apoptosis, and MYC stability.</p><p><strong>Results: </strong>ATE1 was significantly upregulated in breast cancer cells and associated with poor prognosis in early-stage patients. ATE1 depletion selectively impaired viability, proliferation, and migration in breast cancer cells, but not in HMECs. In vivo, ATE1 silencing suppressed tumor growth in xenograft models. Proteomic profiling revealed that ATE1 regulates the cell cycle and survival pathways in a subtype-specific manner, particularly through modulation of the MAPK-MYC-CDK6 axis in luminal T-47D cells. ATE1 stabilized MYC protein via ERK-mediated phosphorylation at Ser62, promoting cell cycle progression and suppressing apoptosis. Rescue experiments confirmed that ATE1's tumor-promoting activity depends on its arginyltransferase function.</p><p><strong>Conclusions: </strong>ATE1 promotes breast cancer progression by enhancing cell proliferation, survival, and migration through MAPK-dependent stabilization of MYC in a lineage-specific context. These findings identify ATE1 as a potential therapeutic target and highlight the relevance of protein arginylation in the molecular heterogeneity of breast cancer.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"390"},"PeriodicalIF":8.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979480","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":"Connexin hemichannel blockade by abEC1.1 disrupts glioblastoma progression, suppresses invasiveness, and reduces hyperexcitability in preclinical models.","authors":"Viola Donati, Chiara Di Pietro, Luca Persano, Elena Rampazzo, Mariateresa Panarelli, Clara Cambria, Anna Selimi, Lorenzo Manfreda, Ana Gabriela de Oliveira do Rêgo, Gina La Sala, Camilla Sprega, Arianna Calistri, Catalin Dacian Ciubotaru, Guang Yang, Francesco Zonta, Flavia Antonucci, Daniela Marazziti, Fabio Mammano","doi":"10.1186/s12964-025-02370-1","DOIUrl":"10.1186/s12964-025-02370-1","url":null,"abstract":"<p><strong>Background: </strong>Connexin (Cx) hemichannels (HCs) contribute to glioblastoma (GBM) progression by facilitating intercellular communication and releasing pro-tumorigenic molecules, including ATP and glutamate.</p><p><strong>Methods: </strong>The efficacy of abEC1.1, a monoclonal antibody that inhibits Cx26, Cx30, and Cx32 HCs, was assessed in vitro by measuring invasion capability, dye and Ca²⁺ uptake, glutamate and ATP release in patient-derived GBM cultures or organoids. Adeno-associated virus (AAV)-mediated antibody gene delivery, or convection-enhanced delivery (CED) of the purified antibody, was used in vivo to test the effect on tumor growth and animal survival, using a syngeneic GBM mouse model. The ability of the antibody to affect glioma-related hyperexcitability was evaluated by patch-clamp recordings in a 2D co-culture model comprising astrocytes and neurons isolated from mouse hippocampi, seeded with GL261 cells.</p><p><strong>Results: </strong>abEC1.1 suppressed GBM cell invasion, reducing gliotransmitter release, and impairing tumor progression. In patient-derived GBM cultures, abEC1.1 significantly decreased cell migration and ATP/glutamate release. In vivo, AAV-mediated antibody gene delivery or CED of the purified antibody reduced tumor burden and prolonged survival in the GL261 syngeneic mouse model of GBM. Furthermore, abEC1.1 mitigated glioma-induced excitatory synaptic activity in the 2D co-culture model, suggesting a dual role in tumor control and hyperexcitability suppression.</p><p><strong>Conclusions: </strong>Our findings establish Cx HC inhibition as a promising therapeutic avenue in GBM and highlight abEC1.1 as a potential candidate for clinical translation.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"391"},"PeriodicalIF":8.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979498","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":"Self-assembled nanoparticle vaccine comprised of multiple epitopes provides robust protective immunity against reoviruses in fish model.","authors":"Fei-Fan Xu, Zhao Zhao, Zhu-Yang Deng, Jia-Lun Tang, Bin Zhu","doi":"10.1186/s12964-025-02411-9","DOIUrl":"10.1186/s12964-025-02411-9","url":null,"abstract":"<p><p>Grass carp reovirus type II (GCRV-II) has inflicted substantial economic damage to aquaculture industry due to highly contagious. To combat epidemic GCRV-II, we rational designed and constructed a multi-epitope nanoparticle vaccine (Pep-Fn) that consisted with cell penetrating peptide (CPP), epitope peptides, cell and grass carp-derived ferritin. Firstly, an anti-GCRV-II phage antibody library was constructed to screen antibodies for outer capsid proteins VP4 and VP35. Ab-1 and Ab-3 were successfully screened and demonstrated high affinity with GCRV-II particles. We further identified five potential epitopes (Pep1-Pep5) on the outer capsid protein recognized by Ab-1 and Ab-3 through protein-protein docking and alanine scanning mutagenesis. Then, a self-assembled nanoparticle displaying the Pep1-Pep5 and CPP on the surface was constructed for Pep-Fn preparation. Benefit from the nano-sized particle structure, Pep-Fn could overcome the body surface barrier and accumulate in the immune organs. Experiments demonstrated that Pep-Fn could effectively stimulate grass carp to produce anti-GCRV-II antibodies via immersion immunization and also provided protective effect against GCRV-II challenge. Collectively, our research provides a new vaccine design strategy for combating GCRV-II, and demonstrates the great potential of protein-based nanoparticle as a platform for GCRV-II vaccine development.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"389"},"PeriodicalIF":8.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979592","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":"Lipid overload meets S-palmitoylation: a metabolic signalling nexus driving cardiovascular and heart disease.","authors":"Jingwen Zhang, Suying Wu, Yuantong Xu, Lei Zhang, Cong Cong, Menghe Zhang, Yonghao Jiang, Yang Liu","doi":"10.1186/s12964-025-02398-3","DOIUrl":"10.1186/s12964-025-02398-3","url":null,"abstract":"<p><p>S-palmitoylation has emerged as a critical integrator of lipid overload and cardiovascular dysfunction. Disordered lipid metabolism inundates endothelial cells, vascular smooth muscle cells and macrophages with triglyceriderich lipoproteins, oxidized LDL and saturated fatty acids, expanding the intracellular palmitoylCoA pool and perturbing redox balance. Protein Spalmitoylation, the reversible attachment of palmitate to cysteine residues, converts excess palmitoylCoA into broad alterations in signalling and membrane dynamics. The FASN-ACSL-ZDHHC axis channel excess fatty acids into palmitoylCoA, which is transferred to pivotal proteins including the lipid transporter CD36, endothelial nitric oxide synthase (eNOS), key ion channels and the pyroptosis effector gasdermin D (GSDMD). Cycles of palmitate addition and removal regulate membrane residency, foam cell formation, nitric oxide production, calcium handling and inflammatory cell death, thereby linking lipid burden to atherosclerotic plaque growth, arrhythmogenic risk, heart failure progression and pulmonary hypertension. Therapeutic targeting of fatty acid uptake, palmitoyltransferases or thioesterases alleviates metabolic overload, restores endothelial reactivity and preserves myocardial viability in experimental models. This review synthesizes mechanistic and preclinical studies to delineate how lipiddriven protein palmitoylation reprograms cardiovascular physiology and pathology.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"392"},"PeriodicalIF":8.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979534","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":"AXL and MERTK facilitate tissue repair in severe acute pancreatitis via a CCR5-dependent neutrophil and macrophage crosstalk.","authors":"Bin Li, Xiuli Zhang, Song Liu, Xiaoyu Guo, Wanyi Lu, Kaixin Peng, Rujuan Liu, Zhigao Chen, Liang Li, Guoyong Hu, Sohail Husain, Xingpeng Wang, Li Wen","doi":"10.1186/s12964-025-02412-8","DOIUrl":"10.1186/s12964-025-02412-8","url":null,"abstract":"<p><p>Severe acute pancreatitis (SAP) is a potentially life-threatening inflammatory disorder of the exocrine pancreas, characterized by massive cell death, which drives the progression and resolution of the disease. However, little is known about the key regulators in the tissue microenvironment that mediate tissue damage and repair. In this study, we discovered that AXL and MERTK in macrophages are responsible for tissue repair and pancreatic inflammation following SAP. Targeted deletion of Axl and Mertk in myeloid cells resulted in impaired phenotypic switch towards pro-resolving macrophage. This impairment is partly due to an accumulation of Cxcr2⁺ neutrophils and its interaction with Mrc1^+/high macrophages likely via CCL4-CCR5 axis. Pancreatic tissue repair was effectively restored by CCR5 inhibition. Collectively, we identify a CCR5-dependent pathway orchestrated by AXL and MERTK in macrophages, which offers a pharmacological target, to promote tissue repair in SAP.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"388"},"PeriodicalIF":8.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979543","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":"Targeting phase separation: a promising treatment option for hepatocellular carcinoma.","authors":"Ziling Zhou, Sikan Jin, Xiaoming Li, Dan Zhang, Shengxi Zhang, He Zhou, Ji Cai, Tao Song, Xianyao Wang, Qinghong Kong, Zhengzhen Tang, Jun Tan, Jidong Zhang","doi":"10.1186/s12964-025-02406-6","DOIUrl":"10.1186/s12964-025-02406-6","url":null,"abstract":"<p><p>The spontaneous phenomena known as liquid-liquid phase separation (LLPS) is caused by weak interactions between substances. Under specific circumstances, macromolecules like proteins and nucleic acids can dynamically aggregate to form biomolecular condensates. This phenomenon offers a novel perspective on the intricate spatiotemporal coordination within living cells. Recent research has shown that LLPS is crucial for the initiation and progression of cancer, mainly by influencing multiple cellular activities such as metabolism, autophagy, stress responses, immune reactions, transcriptional regulation and intracellular signaling pathways, etc. Dysregulation of LLPS significantly affects the proliferation, metastasis, and therapeutic resistance of hepatocellular carcinoma (HCC) cells. Here, we introduce recent advances in understanding how LLPS regulates HCC-associated signaling pathways. Furthermore, we discuss the molecular mechanisms underlying the LLPS of oncogenic signaling molecules and its potential implication. Finally, we summarize several feasible approaches for treating HCC by targeting LLPS. These findings have the potential to establish a novel theoretical framework and therapeutic hypothesis for cancer treatment, thus providing more precise and individualized clinical strategies and significantly enhance patient prognosis and overall survival rates.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"387"},"PeriodicalIF":8.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979547","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":"Whole-gene CRISPR/cas9 library screen revealed targeting STAT6 increased the sensitivity of liver cancer to celecoxib via inhibiting arachidonic acid shunting.","authors":"Chujiao Hu, Zhirui Zeng, Xin Bao, Dahuan Li, Huading Tai, Haohao Zeng, Cheng Luo, Lei Tang, Tengxiang Chen, Shi Zuo","doi":"10.1186/s12964-025-02374-x","DOIUrl":"https://doi.org/10.1186/s12964-025-02374-x","url":null,"abstract":"<p><p>Celecoxib, a selective COX-2 inhibitor, has demonstrated anti-liver cancer effects in various preclinical models and clinical traits. However, prolonged use of celecoxib can lead to drug resistance, necessitating higher doses to maintain efficacy, which often results in severe side effects, limiting its clinical application. This study aimed to identify strategies to overcome celecoxib resistance in liver cancer. CRISPR/Cas9 screening revealed that liver cancer cells compensated for celecoxib treatment by upregulating ALOX and CYP enzymes, facilitating AA metabolism to produce alternative downstream products. STAT6 was identified as a key regulator of ALOX15, ALOX12, and CYP2E1, acting as a resister to celecoxib. Celecoxib stimulation leaded to increased phosphorylation of STAT6, enhanced binding to the promoters of target genes such as ALOX15, and upregulation of downstream gene expression. Knockdown of STAT6 significantly enhanced celecoxib sensitivity in vitro and in vivo by blocking AA shunting mediated by these enzymes. Furthermore, AS1517499, a STAT6 inhibitor, showed strong synergy with celecoxib in liver cancer cells by inhibiting AA shunting. In conclusion, targeting STAT6 enhances the efficacy of celecoxib in liver cancer by suppressing AA shunting. The combination of AS1517499 and celecoxib holds promise as a novel therapeutic strategy for liver cancer.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"384"},"PeriodicalIF":8.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979579","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":"MSP-RON signaling in liver pathobiology and as an emerging therapeutic target: a review of the current evidence.","authors":"Kai Wu, Jia Ji, Jingying Pan, Miaojin Zhu, Jiale Zhang, Ting Sun, Dan Lv, Mudan Wei, Minghai Wang, Hangping Yao","doi":"10.1186/s12964-025-02407-5","DOIUrl":"https://doi.org/10.1186/s12964-025-02407-5","url":null,"abstract":"<p><p>The liver is a crucial organ in the human body and is responsible for various functions, including digestion, detoxification, metabolism, and immune response. Proper hepatic function is vital for maintaining systemic homeostasis, and dysregulation of liver signaling pathways contributes to various diseases. Recepteur d'Origine Nantais (RON) is a transmembrane receptor tyrosine kinase that is activated by macrophage-stimulating protein (MSP) and coordinates cell fate decisions through the activation of downstream signaling cascades. As the predominant source of MSP in humans, the liver establishes a liver-specific MSP‒RON autocrine‒paracrine signaling axis that contributes to hepatic regeneration, metabolism, and immune functions. Extensive research has demonstrated that MSP-RON signaling is involved in steatotic liver diseases, hepatitis, cirrhosis, cholestatic liver disease, and liver cancer, highlighting the importance of RON in the development of liver diseases. This review demonstrates the role of the MSP-RON pathway both in maintaining liver homeostasis and in driving disease onset and progression while exploring its signaling mechanisms and therapeutic potential for liver disorders.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"385"},"PeriodicalIF":8.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979460","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}