Cell Communication and Signaling最新文献

{"title":"Off-target engagement of sotorasib with PPARγ via FABP4: a novel mechanism driving interstitial lung disease.","authors":"Jiaqi Zhang, Jinjin Li, Mengting Cheng, Haiyang Zhou, Xiaochen Zhang, Hao Yan, Zhifei Xu, Bo Yang, Qiaojun He, Zizheng Gao, Xueqin Chen, Peihua Luo","doi":"10.1186/s12964-025-02425-3","DOIUrl":"10.1186/s12964-025-02425-3","url":null,"abstract":"","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"416"},"PeriodicalIF":8.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214575","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":"Investigation of the heterogeneity of cancer cells using single cell Ca²⁺ profiling.","authors":"Amélie E Bura, Camille Caussette, Maxime Guéguinou, Dorine Bellanger, Alison Robert, Mathilde Cancel, Margot Lacouette-Rata, Gaëlle Fromont, Christophe Vandier, Karine Mahéo, Thierry Brouard, David Crottès","doi":"10.1186/s12964-025-02417-3","DOIUrl":"10.1186/s12964-025-02417-3","url":null,"abstract":"<p><strong>Background: </strong>Calcium (Ca²⁺) is an essential second messenger that controls numerous cellular functions. Characteristics of intracellular Ca²⁺ oscillations define Ca²⁺ signatures representatives of the phenotype of a cell. Oncogenic functions such as migration, proliferation or resistance to chemotherapy have been associated with aberrant Ca²⁺ fluxes. However, the identification of Ca²⁺ signatures representatives of the oncogenic properties of cancer cells remains to be addressed.</p><p><strong>Methods: </strong>To characterize and investigate the heterogeneity of oncogenic Ca²⁺ signatures, we proposed an unbiased scalable method that combines single cell calcium imaging with graph-based unsupervised and artificial neural networks.</p><p><strong>Results: </strong>From an initial dataset of 27,439 agonist-induced Ca²⁺ responses elicited in a panel of 16 prostate and colorectal cancer cell lines, we discriminate 26 clusters of Ca²⁺ responses using unbiased unsupervised clustering. From these clusters, we generate Ca²⁺ signatures for each cancer model allowing to functionally compare different cancer models. In parallel, we propose supervised neural network models predicting characteristics of a single cancer cell based on its profile of Ca²⁺ responses. We applied those methods to characterized a remodeling of Ca²⁺ signatures associated with acquired docetaxel resistance (12,911 cells) or in the course of the interaction of cancer cells with fibroblasts (34,676 cells). At single cell level, our supervised neural network succeeded to identify docetaxel-resistant cancer cells and to distinguish cancer cells from fibroblasts on the sole measure of agonist-induced Ca²⁺ response.</p><p><strong>Conclusions: </strong>Our method demonstrates the potential of Ca²⁺ profiling for discriminating cancer cells and predict their phenotypic characteristics at single cell level, and provides a framework for researchers to investigate the remodeling of the Ca²⁺ signature during cancer development.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"413"},"PeriodicalIF":8.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214481","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":"A novel role of liquid plasma (LP) induced RONS triggers the endoplasmic reticulum stress response and is associated with GSDME-mediated pyroptosis in anaplastic thyroid cancer.","authors":"Eun Jong Ji, Se Hyun Yeou, Sung Un Kang, Chul-Ho Kim","doi":"10.1186/s12964-025-02397-4","DOIUrl":"10.1186/s12964-025-02397-4","url":null,"abstract":"<p><strong>Background: </strong>Anaplastic thyroid cancer (ATC) is an aggressive cancer with a poor prognosis and resistance to multimodal treatments. Various drugs have a short response time and are likely ineffective against ATC. Therefore, new molecular therapies and novel targets are needed. Recently, plasma medicine has been used in biomedical applications on skin, wound healing, and cancer treatment of the liver, colon, and head and neck. However, direct plasma has difficulty treating, sustaining, and permeating the various affected areas. In this study, we prepared Liquid-type plasma (LP) and investigated their effect on ATC cells.</p><p><strong>Methods: </strong>The physicochemical properties and ion composition of liquid-type plasma (LP) were analyzed using ion chromatography, after which anaplastic thyroid cancer (ATC) cell lines, primary fibroblasts, and keratinocytes were employed to evaluate its biological effects. Cell viability, apoptosis/pyroptosis, and redox status were assessed by biochemical assays, flow cytometry, and Western blotting, while transcriptomic profiling (RNA-seq) with gene ontology analysis was performed to identify regulated pathways. Finally, an orthotopic ATC xenograft mouse model was used to validate the therapeutic efficacy of LP in vivo.</p><p><strong>Results: </strong>The pH of LP decreased to 1.92 And remained stable for 14 days, while electrical conductivity was measured at 4.76 mS/cm without significant Change. Additionally, the oxidation-reduction potential was maintained at 652.2 mV for 14 days. Cl, NO2, and NO3 Anions were identified as 62 ppb, 12.6 ppm, And 1044 ppm, respectively, And Na, K, And Ca cations were measured as 169 ppb, 27 ppb, And 25 ppb, respectively. Therefore, a significant concentration of nitrogen species is involved in the LP, which is attributed to the secondary reaction of reactive oxygen species (ROS) formed during this treatment. LP reduced ATC cell viability, which exhibited cell swelling and bubble formation morphologically. Gasdermin E (GSDME) was cleaved by LP and induced pyroptosis in ATC cells. Inhibiting caspase activity and knock down of GSDME showed reduced caspase-3 dependent cleavage of GSDME, consequently increasing cell viability and decreasing lactate dehydrogenase release. LP enhanced the production of intracellular RONS and induced phosphorylation of IRE1α that is associated with endoplasmic reticulum (ER) stress. Therefore, GSDME-mediated LP induced pyroptosis downstream of the RONS/ER stress pathway and activated caspase-3. We then confirmed tumor shrinkage through in vivo and histological analysis, with a focus on the increasing GSDME-N terminal.</p><p><strong>Conclusion: </strong>LP induces pyroptosis via GSDME activation and RONS generation in vitro and in vivo in ATC models, suggesting a novel mechanism and indicating a potential chemotherapeutic approach for the treatment of ATC.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"411"},"PeriodicalIF":8.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214487","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":"TRAP1 inhibits KANSL3 acetylation to alleviate mitochondrial dysfunction by promoting mitophagy in cardiomyocytes under diabetic conditions.","authors":"Xiaoyu Zhang, Shiyao Cheng, Wenxin Li, Xintian Xu, Xiaojing Huang, Zhichong Chen, Qinglang Li, Wanjing Huang, Lingxiao Zhang, Mao Ouyang","doi":"10.1186/s12964-025-02402-w","DOIUrl":"10.1186/s12964-025-02402-w","url":null,"abstract":"","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"414"},"PeriodicalIF":8.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214640","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":"Tumor necrosis factor promotes doublecortin-like kinase 1 expression and cellular reprogramming in intestinal epithelial cells leading to neoplastic transformation.","authors":"Lin Huang, Tianqi Li, Xu Huang, Xiaoxi Chen, Yuanyuan Ju, Lili Xu, Chunhua Ma, Yumei Tao, Yonghong Yang, Xiaoyun Bian, Mark M Huycke, Xingmin Wang","doi":"10.1186/s12964-025-02400-y","DOIUrl":"10.1186/s12964-025-02400-y","url":null,"abstract":"","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"415"},"PeriodicalIF":8.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214625","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":"Review: Progress of the NLRP3 inflammasome in tumours and perspectives for cholangiocarcinoma.","authors":"Zhaoqin Zhuo, Yuwei Xie, Hao Zou, Bin Tan, Qian Dong, Bingzi Dong, Chengzhan Zhu","doi":"10.1186/s12964-025-02416-4","DOIUrl":"10.1186/s12964-025-02416-4","url":null,"abstract":"<p><p>The NLRP3 inflammasome is a multi-protein complex that mediates intense inflammatory responses. Its activation and function are influenced by various factors, including the recognition of pathogen-associated molecular patterns and damage-associated molecular patterns, cellular stress responses, and metabolic disorders. Recent research has extensively studied the role of the NLRP3 inflammasome in tumors. Findings indicate that tumor cells and macrophages can regulate the activation of the NLRP3 inflammasome, promoting tumor development and progression. Conversely, the NLRP3 inflammasome can also exhibit anti-tumor effects through immune cells, such as dendritic cells. This has led to the development of treatment strategies, creating a comprehensive treatment system that includes sensitizers for radiotherapy and chemotherapy, inhibitors of the NLRP3 inflammasome pathway, and direct targeting of the NLRP3 inflammasome.Cholangiocarcinoma is a highly invasive and heterogeneous malignant tumor. Due to its non-specific symptoms, patients often present with advanced stages of the disease, and the mortality rate continues to rise annually. A deeper exploration of the mechanisms underlying cholangiocarcinoma's occurrence and development is essential for improving diagnosis and treatment strategies. The application of multi-omics analysis in cholangiocarcinoma research lays a foundation for understanding its pathogenesis and potential treatments. This article systematically reviews the latest advancements in NLRP3 inflammasome research, including its regulatory mechanisms, role in promoting tumor development, and effects in anti-tumor immunotherapy. Additionally, by summarizing the mechanisms involved in cholangiocarcinoma, we hypothesize that the NLRP3 inflammasome may play a significant role in the occurrence and development of cholangiocarcinoma. Therefore, we conduct a multi-angle analysis of the potential relationship between the two and propose a hypothesis model. The goal of this article is to explore the role of the NLRP3 inflammasome in tumors and its potential relationship with cholangiocarcinoma, offering new insights for research on the link between cholangiocarcinoma-related inflammation and the disease itself.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"405"},"PeriodicalIF":8.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208433","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":"A comparative proteomic, transcriptomic and glycomic analysis of extracellular vesicle isolation techniques highlights ExoGAG efficiency for a more complete identification of breast milk molecular signaling pathways.","authors":"María Pereira-Hernández, Rosaura Picáns-Leis, María E Vázquez-Mosquera, Nerea Lago-Baameiro, Pedro Fortes-González, Laura López-Valverde, Ana Barcia de la Iglesia, Laura Núñez-González, Susana B Bravo, María Pardo, María L Couce, Miguel A Garcia-Gonzalez","doi":"10.1186/s12964-025-02390-x","DOIUrl":"10.1186/s12964-025-02390-x","url":null,"abstract":"","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"412"},"PeriodicalIF":8.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214509","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":"PLA2 driven lipid signaling drives ARMS tumorigenic cell properties.","authors":"Amogh Gupta, Bharathi Ramanathan, Dipanwita Das, Aiswariya Vadivellu, Amos Hong Pheng Loh, Reshma Taneja","doi":"10.1186/s12964-025-02409-3","DOIUrl":"10.1186/s12964-025-02409-3","url":null,"abstract":"<p><strong>Background: </strong>Advancements in chemotherapy have improved outcomes for rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children. However, relapse-free survival rates remain below 20% in metastatic alveolar rhabdomyosarcoma (ARMS). Tumor-initiating cells (TICs) drive recurrence. Targeting this pool of cells has been shown to reduce relapse rates and metastasis in various cancers. Emerging evidence implicates lipid metabolism in supporting stem-like properties in cancer. However, TICs remain poorly characterized in ARMS. This study investigates the transcriptomic and metabolic profile of TICs in ARMS.</p><p><strong>Methods: </strong>Transcriptomic and lipidomic profiling were performed on tumorsphere-derived and adherent cells from ARMS cells. Differential expression of metabolic genes and lipid species was assessed via RNA-Sequencing and mass spectrometry. Functional dependence on Phospholipase A2 (PLA2) signaling was tested on TICs in vitro and in vivo. Seahorse assays were used to measure glycolytic and mitochondrial flux. Statistical significance was determined using Student's t-test or one-way ANOVA.</p><p><strong>Results: </strong>Transcriptomic analysis of ARMS tumorspheres showed upregulation of lipid metabolism especially different PLA2 enzyme subtypes, and suppression of glycolytic gene expression. Lipidomic analyses revealed enrichment of linoleic acid-derived triglycerides and lysophospholipids, paralleled by increased PLA2 activity. Tumorspheres also showed elevated expression of lipid storage regulators PPARG and CD36 and correspondingly, significant lipid droplet accumulation. Inhibition of PLA2 with Darapladib reduced tumorsphere formation and cellular motility in vitro and tumor volume in vivo. These defects were rescued by exogenous linoleic acid (LA) supplementation, implicating PLA2-driven lipid signalling in TIC maintenance. Interestingly, TICs display high metabolic flexibility in energy consumption, as neither glycolysis nor fatty acid oxidation (FAO) inhibition significantly impaired tumorsphere formation.</p><p><strong>Conclusions: </strong>PLA2-mediated lipid remodelling supports TIC by promoting linoleic acid-linked lipid signalling. PLA2 inhibition impairs self-renewal, motility, and tumorigenic potential, highlighting it as a promising therapeutic target in ARMS. These findings uncover lipid remodelling as a key metabolic adaptation in ARMS TICs, independent of canonical energy pathways, with implications for targeting the stem-like compartment in pediatric sarcomas.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"404"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208453","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":"The aggressive colorectal cancer subtype marker HTR2B has a dual role depending on the tumor microenvironment.","authors":"Idan Carmi, Adrián Orosz, Szabolcs Hajdó, Anikó Zeöld, Tamás Hegedűs, Dóra Kelemen-Győri, Julianna Pozsár, Tamás Tölgyes, Zoltán Wiener","doi":"10.1186/s12964-025-02395-6","DOIUrl":"10.1186/s12964-025-02395-6","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the second-third most frequent cancer type in the Western countries, with significant inter- and intra-patient cellular heterogeneity. The transcriptomics-based CRC classification identified a cluster of patients with epithelial-mesenchymal transition (EMT), the accumulation of fibroblasts, and dismal prognosis. Although the serotonin receptor HTR2B is thought to be one of the epithelial markers of this aggressive CMS4 subgroup, its precise role in CRC tumorigenesis is still largely unknown. By using patient-derived organoids (PDO), we prove the heterogeneous expression of this receptor that is under the control of the mTOR pathway. Unfavorable conditions, applying the clinically used 5-fluorouracil, co-culturing with fibroblasts, and collagen-I accumulation in the extracellular matrix (ECM) increased the number of HTR2B + cells. Interestingly, whereas stimulating HTR2B had no effect on PDOs under normal conditions, it reduced cellular survival under unfavorable conditions when carbohydrates were lacking. In contrast, serotonin and an HTR2B agonist induced invasion of HTR2B + tumor cells only in collagen-I, representing a permissive ECM for cellular migration. CRC cells positive for HTR2B also expressed the NOTCH3 receptor and NOTCH target genes at a higher intensity than cells with low HTR2B levels. Similar to HTR2B + organoids, NOTCH3 + PDOs had increased EMT markers and HTR2B levels. Furthermore, blocking NOTCH activity inhibited the serotonin-induced invasion. Collectively, our results show that the serotonin receptor HTR2B marks a CRC cell population with increased proliferative capacity, invasive potential, and partial EMT, and they highlight the critical role of ECM in shaping the effect of serotonin in CRC.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"403"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208455","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":"ZDHHC21-driven S-palmitoylation of Themis regulates the function of T cells and maintains homeostatic balance.","authors":"Caiyun Meng, Xinchen Dai, Liting Sun, Dan Huang, Xinrui Xu, Yiwen Cheng, Weiguo Zhang","doi":"10.1186/s12964-025-02396-5","DOIUrl":"10.1186/s12964-025-02396-5","url":null,"abstract":"","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"401"},"PeriodicalIF":8.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201913","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}