Cell Communication and Signaling最新文献

{"title":"Matrix stiffness-induced IKBKE and MAPK8 signaling drives a phenotypic switch from DCIS to invasive breast cancer.","authors":"Feifei Yan, Sara Göransson, Helene Olofsson, Christos Vogiatzakis, Anagha Acharekar, Staffan Strömblad","doi":"10.1186/s12964-025-02276-y","DOIUrl":"10.1186/s12964-025-02276-y","url":null,"abstract":"<p><p>Ductal carcinoma in situ (DCIS) is not life threatening unless it transitions into invasive breast cancer (IBC). However, although breast cancer cell exposure to matrix stiffening in vitro phenotypically mimics the DCIS to IBC switch, the molecular changes driving this switch remains unclear. Here, breast cancer cell kinome activity profiling suggested matrix stiffness-upregulation of 53 kinases, among which 16 kinases were also regulated by integrin β1. Functional validation identified matrix stiffness-activation of inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE) and mitogen-activated protein kinase 8 (MAPK8) signaling as critical for the stiffness-driven IBC phenotype, including for cell proliferation. The IKBKE-inhibitor Amlexanox, clinically utilized for aphthous ulcers, as well as the MAPK8 inhibitor JNK-IN-8, reinstalled the DCIS-like phenotype of breast cancer cells on high matrix stiffness. This suggests that IKBKE and/or MAPK8 inhibitors could enhance the arsenal of treatments to prevent or treat breast cancer.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"269"},"PeriodicalIF":8.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227759","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":"Functionalized exosomes for targeted therapy in cancer and regenerative medicine: genetic, chemical, and physical modifications.","authors":"Salar Ghaffari Gabaran, Navid Ghasemzadeh, Maryam Rahnama, Erkan Karatas, Ali Akbari, Jafar Rezaie","doi":"10.1186/s12964-025-02268-y","DOIUrl":"10.1186/s12964-025-02268-y","url":null,"abstract":"<p><strong>Background: </strong>Extracellular vesicles (EVs), such as exosomes, have been extensively discovered for their function in various diseases and potential therapeutic properties. In this review, we aimed to describe the therapeutic roles of functionalized exosomes in cancer and regenerative medicine.</p><p><strong>Methods: </strong>In this review study, we studied numerous articles over the past two decades published on the application of exosomes in different diseases, as well as on perspectives and challenges in this field.</p><p><strong>Results: </strong>Recent advancements have shown that exosomes can be used as a drug delivery system. However, this approach faces challenges such as low efficiency and non-targeting effects. Different methods, including genetic, chemical, and physical modifications, are used to functionalize exosome surfaces to address these limitations. In some cases, a combination of modification methods has been used to produce smart exosomes. Different therapeutic agents have been inserted on exosome surfaces by different modification methods. These functionalized exosomes can effectively deliver therapeutic agents to target cells. A growing body of evidence shows that functionalized exosomes are promising for cancer therapy and regenerative medicine. They can not only effectively deliver therapeutic agents to cancer cells, inhibiting tumorigenesis, but also efficiently contribute to tissue repair and regeneration by increasing cell proliferation and angiogenesis. In this review, we discuss different modification methods used to functionalize exosomes and related studies. In addition, we describe the application of functionalized exosomes in cancer and regeneration, along with challenges and perspectives.</p><p><strong>Conclusions: </strong>Although functionalized exosomes show promising results, further studies are essential for the clinical translation of these exosomes.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"265"},"PeriodicalIF":8.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227758","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":"Unlocking the life code: a review of SnoRNA functional diversity and disease relevance.","authors":"Yinghui Li, Xinzhe Chen, Shudan Xiao, Haoxuan Wang, Bo Li, MeiHua Zhang, Kun Wang","doi":"10.1186/s12964-025-02274-0","DOIUrl":"10.1186/s12964-025-02274-0","url":null,"abstract":"<p><p>Nucleolar small RNA (snoRNA), as a class of non-coding RNAs, play a crucial role in eukaryotic cells. They are widely involved in post-transcriptional modifications of ribosomal RNAs, including methylation and pseudouridylation, precisely regulating the process of ribosome biogenesis, ensuring the integrity of ribosome structure and function, and thereby guaranteeing the accuracy and efficiency of protein synthesis. snoRNAs not only maintain cell growth, proliferation, and differentiation under normal physiological conditions but also have abnormal expression closely associated with various diseases, such as cancer, cardiovascular diseases and neurodegenerative diseases. In recent years, with the innovation of research techniques, there has been a deeper exploration of the biosynthesis pathways, functional mechanisms of snoRNAs, and their potential value in disease diagnosis and treatment. This review comprehensively summarizes the structural characteristics, classification systems, biological functions, and disease associations of snoRNAs, and looks forward to future research directions, aiming to provide a systematic reference for further exploration of the mysteries of snoRNAs in related fields.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"266"},"PeriodicalIF":8.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227781","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":"Apoptosis-inducing factor (AIF) at the crossroad of cell survival and cell death: implications for cancer and mitochondrial diseases.","authors":"Tran Ngoc Anh Nguyen, Hong-Toan Lai, Romain Fernandes, Filippo G Dall'Olio, Camille Blériot, Tap Ha-Duong, Catherine Brenner","doi":"10.1186/s12964-025-02272-2","DOIUrl":"10.1186/s12964-025-02272-2","url":null,"abstract":"<p><p>Apoptosis-inducing factor (AIF), a mitochondrial NAD(P)H-dependent oxidoreductase, was initially studied as a cell death inducer in a process later named parthanatos. However, it has been revealed that AIF also participates in mitochondrial bioenergetics through interaction with its partner coiled-coil-helix-coiled-coil-helix domain containing 4 (CHCHD4) and involvement in mitochondrial protein import. These dual roles place AIF between pro-survival and pro-death cell fate decisions. In this review, we first describe the structure and the dual functions of AIF, highlighting its structure-function relationships. We then report previously identified AIFM1 mutations and their clinical phenotypes. Finally, we discuss the relevance of AIF in cancer and the potential of targeting this protein for the treatment of cancer.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"264"},"PeriodicalIF":8.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227757","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":"Trem2 regulates microglial migratory responses via type I interferon signaling during photoreceptor degeneration.","authors":"Jincan He, Wenchuan Zhou, Jing Li","doi":"10.1186/s12964-025-02261-5","DOIUrl":"10.1186/s12964-025-02261-5","url":null,"abstract":"<p><strong>Background: </strong>Various functions of activated microglia play crucial roles in the progression of retinitis pigmentosa (RP). This study aims to investigate the mechanisms underlying microglial migratory responses and phagocytic activity and their effects on photoreceptor degeneration.</p><p><strong>Methods: </strong>Trem2-deficient rd10 mice (Trem2^-/-:rd10) were used in this study. N-methyl-N-nitrosourea (MNU)-induced retinal degeneration was established in microglia-specific Trem2 overexpression mice (Tmem119^CreERT2:Rosa26^{CAG - LSL-Trem2}). IFN-α/β receptor I (IFNAR1) neutralizing antibody was used to achieve type I interferon (IFN-I) signaling blockade. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), immunofluorescent staining and western blot analysis were used to assess microglial responses and photoreceptor cell apoptosis. Microglia were purified with CD11b MicroBeads. Transcriptomic profiles of the whole retina were generated and analyzed.</p><p><strong>Results: </strong>Progressive photoreceptor cell death and sustained microglial migratory responses were observed throughout the degeneration process in rd10 mice and MNU model. Trem2-deficient microglia displayed impaired migratory responses and subsequent phagocytosis, affecting photoreceptor cell survival at different stages of rd10 mice. Conversely, microglia-specific Trem2 overexpression mice showed enhanced microglial migration following MNU treatment. Furthermore, we found IFN-I signaling pathway was associated with microglial migration, which was regulated by TREM2 expression. Exogenous IFN-I blockade weakened microglial migration and reversed the effects of photoreceptor cell death caused by Trem2 overexpression.</p><p><strong>Conclusions: </strong>Our findings demonstrated the divergent roles of Trem2-mediated microglial migratory responses and phagocytic activity at different stages of RP-featured retinal degeneration models. We identified the link between Trem2 and IFN-I signaling in microglia and provided a potential microglia-associated target for RP therapy.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"267"},"PeriodicalIF":8.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227780","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 immunosuppressive effect of glucocorticoids in human primary T cells is mainly mediated via a rapid inhibition of the IL-2/IL-2R signaling axis.","authors":"L Tatiana Albarracin Melo, Nekruz Abdulkhakov, Irina Han, Ali El-Bizri, Monika Brunner-Weinzierl, Burkhart Schraven, Luca Simeoni","doi":"10.1186/s12964-025-02266-0","DOIUrl":"10.1186/s12964-025-02266-0","url":null,"abstract":"<p><strong>Background: </strong>Glucocorticoids (GCs) are highly effective anti-inflammatory drugs that suppress T-cell activation, cytokine production, and T-cell proliferation. Nevertheless, at which molecular level and how fast GCs exert their immunosuppressive effect in T cells still remains elusive, as inconsistent genomic and non-genomic mechanisms of action have been proposed. One model postulates that GCs quickly inhibit proximal T-cell receptor (TCR) signaling via a non-genomic mechanism, whereas others have shown a strong inhibition of interleukin-2 (IL-2) transcription at later stages of T-cell activation. Due to their therapeutic significance, we have decided to shed light onto this issue and investigated how fast and at which level GCs inhibit T-cell activation by analyzing TCR and IL-2 signaling.</p><p><strong>Methods: </strong>We utilized primary human T cells isolated from healthy donors, which were stimulated with immobilized CD3/CD28 antibodies. These cells were treated with three different GCs, diflorasone, dexamethasone, and prednisolone.</p><p><strong>Results: </strong>Analyses of signaling kinetics revealed that GCs did not affect early TCR signaling as suggested by the normal phosphorylation levels of lymphocyte-specific protein tyrosine kinase (Lck), zeta-chain-associated protein kinase 70 (Zap70), linker for activation of T cells (LAT), and unchanged Ca²⁺ influx. Conversely, we found that GCs strongly and rapidly suppressed the activation of the Janus kinase (Jak)/ signal transducer and activator of transcription (STAT) pathway within 4-6 h upon CD3/CD28 stimulation in primary human T cells. This observation was in line with a strong inhibition of cytokine production and with the impaired upregulation of the IL-2 receptor (IL-2R) upon GC treatment, thus resulting in the abrogation of T-cell proliferation.</p><p><strong>Conclusions: </strong>Our study, by showing that GCs rapidly suppress the IL-2/IL-2R expression and signaling without significantly affecting proximal TCR signaling, has highlighted a clear mechanism of action of GCs that contributes to their therapeutic efficacy.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"268"},"PeriodicalIF":8.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227779","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":"Enhancing intestinal epithelial microtubule stability could alleviate IBD symptoms.","authors":"Fangying Yang, Zhengxiao He, Xiumei Pan, Shuping Xie, Xinhua Liang, Lanlan Geng, Wanfu Xu, Sitang Gong","doi":"10.1186/s12964-025-02264-2","DOIUrl":"10.1186/s12964-025-02264-2","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory bowel disease (IBD) is characterized by epithelial barrier dysfunction, where in the cytoskeleton, especially actin microfilaments and intermediate filaments, has been extensively investigated for its critical role in maintaining the structural integrity of the epithelial barrier. However, the specific contribution of microtubules to this process remains unknown.</p><p><strong>Methods: </strong>In this study, we analyzed the expression of acetylated α-tubulin (Ac-α-tubulin), a marker of stable microtubule structures, in colonic tissues from IBD patients and healthy controls using immunofluorescence. We also employed dextran sulfate sodium (DSS) to induce colitis in murine models and stimulated Caco-2 cells with tumor necrosis factor-alpha (Tnfα) to elucidate the subsequent alterations in microtubule dynamics. We subsequently evaluated the impact of microtubule-associated protein kinase 2 (MARK2) deficiency on microtubule dynamics, epithelial permeability, and inflammation. This was accomplished using both stable MARK2 knockdown Caco-2 cell lines and intestinal epithelial-specific MARK2 conditional knockout (MARK2^vil1) mice. Additionally, we explored whether treatment with the microtubule stabilizer paclitaxel (PTX) and the SIRT2 selected inhibitor AGK2 could reverse these phenotypic changes.</p><p><strong>Results: </strong>Our findings revealed a significant reduction in Ac-α-tubulin expression in both IBD patient tissues and the DSS-induced colitis model. Treatment with PTX significantly enhanced Ac-α-tubulin levels and mitigated colitis symptoms in DSS-induced mice. Furthermore, MARK2 knockdown decreased Ac-α-tubulin expression and increased paracellular permeability, which could be reversed by AGK2 or PTX treatment.</p><p><strong>Conclusion: </strong>This study provides new insights into the pathogenesis of IBD by elucidating the role of microtubules in epithelial barrier disruption. Our findings propose microtubule-modulating therapeutics as a potential novel treatment strategy for IBD, highlighting the importance of stabilizing microtubules to restore epithelial integrity and reduce inflammation.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"263"},"PeriodicalIF":8.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217653","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":"Adipocyte/Tumor cell crosstalk via IGF-1/TXNIP axis promotes malignancy and endocrine resistance in breast cancer.","authors":"Amanda Caruso, Felice Maria Accattatis, Cinzia Giordano, Luca Gelsomino, Piercarlo Del Console, Maria Francesca Fiorita, Balazs Gyorffy, Laura Bianchi, Alfonso Carleo, Rossana De Salvo, Bruno M Simões, Robert B Clarke, Lorenzo Memeo, Cristina Colarossi, Eleonora Aiello, Francesco Conforti, Suzanne A W Fuqua, Matilde Todaro, Giorgio Stassi, Catia Morelli, Diego Sisci, Daniela Bonofiglio, Stefania Catalano, Sebastiano Andò, Ines Barone","doi":"10.1186/s12964-025-02262-4","DOIUrl":"10.1186/s12964-025-02262-4","url":null,"abstract":"","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"262"},"PeriodicalIF":8.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217642","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 subset of Orai1α and Orai1β subunits heteromerizes to form CRAC channels.","authors":"Jose J Lopez, Isaac Jardín, Vanesa Jiménez-Velarde, Sandra Alvarado, Alvaro Macías-Díaz, Joel Nieto-Felipe, Francisco J Martín-Romero, Tarik Smani, Juan A Rosado","doi":"10.1186/s12964-025-02271-3","DOIUrl":"10.1186/s12964-025-02271-3","url":null,"abstract":"<p><strong>Background: </strong>Ca²⁺ release-activated Ca²⁺ (CRAC) channels are highly Ca²⁺ selective plasma membrane channels formed by the hexameric assembly of Orai subunits, with a predominant role for Orai1. Two Orai1 variants have been identified, Orai1α, which comprises 301 amino acids, and a short variant, Orai1β, lacking the first N-terminal 63 or 71 amino acids; however, little is known about their possible heteromerization to form CRAC channels. Here we show that Orai1α and Orai1β exhibit different lipid raft distributions in resting cells when expressed individually, likely due to the presence of a caveolin-binding domain exclusively in Orai1α. However, when both variants are co-expressed, they show a similar distribution predominantly in the lipid raft domains, indicating potential interaction between the two Orai1 forms.</p><p><strong>Methods: </strong>A lipid raft isolation protocol in combination with Western blotting assay was conducted to detect the expression of each Orai1 variants in the isolated membrane fractions. Ca²⁺ mobilization was determined using fura-2 and G-GECO1.2 fused to Orai1α fluorescence. Evidence of physical interaction between both Orai1 variants was provided using co-immunoprecipitation, APEX2 peroxidase-catalyzed proximity labeling, Förster resonance energy transfer (FRET) and super-resolution microscopy.</p><p><strong>Results: </strong>Our results indicate that Orai1α and Orai1β exhibit different lipid raft partitioning in resting cells when expressed individually, likely attributed to the presence of a caveolin-binding domain in Orai1α. However, when both variants are co-expressed, they show a similar distribution predominantly in the lipid raft domains, indicating potential interaction between the two Orai1 forms. Expression of a dominant-negative Orai1β mutant has been found to interfere with Orai1α-mediated Ca²⁺ entry. Using co-immunoprecipitation, APEX2 peroxidase-catalyzed proximity labeling, Förster resonance energy transfer (FRET) and super-resolution microscopy our results indicate that there is certain interaction between Orai1α and Orai1β although both variants form mostly independent channels.</p><p><strong>Conclusions: </strong>Our results indicate that while Orai1α and Orai1β mostly form separate CRAC channels, a small subset of both Orai1 variants combine to form heteromeric channels. These findings provide new insights on the nature of CRAC channels.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"260"},"PeriodicalIF":8.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210333","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":"Natural flavonoids combat cytosolic MRSA by potentiating phagosome acidification.","authors":"Xiaohui Si, Ruoyi Lv, Ziwen Cai, Zhigang Sun, Wenjing Zhang, Jing Wang, Xiaoye Liu","doi":"10.1186/s12964-025-02252-6","DOIUrl":"10.1186/s12964-025-02252-6","url":null,"abstract":"<p><p>The emergence of multidrug-resistant bacteria (MDR), particularly in cytosolic methicillin-resistant Staphylococcus aureus (MRSA) are causing substantial infections and posing an urgent global threat to public health. The era of antibiotic resistant has hindered the development of antibiotics that solely target bacteria, highlighting the need for alternative therapeutic strategies. Host-acting therapies are emerging as a dominant approach to address the shortage of novel antibiotics and prevent novel-resistant bacteria. Herein, we explored the modes of action of five flavonoids that combat cytosolic MRSA through host-acting antibacterial effects. Both in vitro and in vivo models demonstrated the efficacy of flavonoids in combating cytosolic MRSA lung infections. Transcriptomic and proteomic analyses revealed that the antibacterial targets of these flavonoids are linked to the phagosome pathway. Mechanistic studies further showed that flavonoids enhance lysosomal acidification, identifying it as a viable target for host-acting antibacterial drugs. These findings suggest that flavonoid treatments represent a promising host-acting therapeutic strategy for combating cytosolic MRSA infections.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"259"},"PeriodicalIF":8.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210335","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}