Frontiers in Cell and Developmental Biology最新文献

{"title":"Relative suppression of pyroptosis- and necroptosis-related transcriptional programs and enrichment of ferroptosis-related signatures are associated with fatal sepsis: multi-cohort bulk and single-cell transcriptomic evidence.","authors":"Jing Xu, Peng Wang, Mingzhao Xu","doi":"10.3389/fcell.2026.1885384","DOIUrl":"https://doi.org/10.3389/fcell.2026.1885384","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a life-threatening syndrome caused by a dysregulated host response to infection and remains a major cause of mortality in critically ill patients. Multiple forms of programmed cell death (PCD) may contribute to immune dysregulation and organ injury, but their transcriptional patterns across disease severity and outcome remain incompletely defined.</p><p><strong>Methods: </strong>We performed an integrative transcriptomic analysis of five public sepsis cohorts, including single-cell RNA sequencing datasets GSE167363 and GSE151263 and three bulk transcriptomic cohorts. Primary outcome analyses focused on cohort-defined fatal sepsis (28-day non-survivors in GSE65682 and the deposited sepsis-death group in GSE63042), whereas pneumonia/ARDS comparisons were treated as secondary exploratory analyses. PCD-related transcriptional programs were evaluated across clinical groups and immune-cell populations. Six candidate genes were further assessed by RT-qPCR in LPS-stimulated RAW264.7 and THP-1 cells as targeted <i>in vitro</i> transcriptional validation.</p><p><strong>Results: </strong>In GSE65682, 28-day non-survivors showed lower pyroptosis, necroptosis and apoptosis program scores but higher ferroptosis scores than survivors, and higher pyroptosis scores were associated with better 28-day survival. GSE154918 instead showed broader increases in PCD-related program scores from healthy controls to infection/sepsis groups, reflecting a disease-versus-control contrast rather than an outcome contrast. In the LPS model, CASP1, RIPK3 and NLRP3 were upregulated, whereas SIRT1, BCL2 and HIF1A were downregulated. These cell experiments assessed acute inflammatory transcriptional responsiveness and were not intended to reproduce the mortality-associated direction observed in patient cohorts.</p><p><strong>Conclusion: </strong>Multi-cohort analyses identified outcome-associated PCD transcriptional patterns in sepsis, including relative suppression of pyroptosis- and necroptosis-related programs and enrichment of ferroptosis-related signatures in non-survivors. The LPS experiments provide complementary mRNA-level evidence that selected PCD genes are transcriptionally responsive to inflammatory stimulation, but they do not constitute directional or functional validation of the fatal-sepsis signature. Functional and prospective clinical validation remains required.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1885384"},"PeriodicalIF":5.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166092","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":"Cancer degronopathies and protein-fate biomarkers in drug resistance and cancer progression: signalling mechanisms, measurement and translational limits.","authors":"Jiaxin Li, Shuhan Liu, Lu Fu, Qifu Bo, Yujie Bai, Xiangpeng Dai","doi":"10.3389/fcell.2026.1960932","DOIUrl":"https://doi.org/10.3389/fcell.2026.1960932","url":null,"abstract":"<p><p>Drug resistance remains a major barrier to durable targeted therapy, and cancer progression often reflects rewiring of signalling pathways that control protein stability. Dysregulation of the ubiquitin-proteasome system, including failure of degron-dependent substrate recognition, can stabilise oncogenic proteins, accelerate tumour-suppressor loss and generate treatment-dependent protein states. Yet clinical interpretation commonly relies on genotype or steady-state abundance, neither of which directly identifies the degradation rate or route of a specific substrate. In this critical narrative review, we use cancer degronopathy as a restricted operational term for tumour-relevant alterations in degron-dependent recognition, rather than as an established disease or diagnostic class. Through contrastive analysis of four endogenous modules (SPOP; FBXW7 versus CTNNB1; KEAP1-NFE2L2-CUL3; and VHL-HIF), together with drug-induced degradation, we examine how altered protein fate intersects with signalling pathways implicated in cancer progression, intrinsic or acquired drug resistance and therapeutic response. We trace each candidate biomarker from the initiating tumour event and substrate-specific fate change to patient-compatible measurement, analytical performance and intended clinical use. The analysis shows that SPOP effects vary with allele, substrate, lineage and assembly; FBXW7 reader defects and CTNNB1 cis-acting escape require different analytes; and pooled KEAP1-axis states and cross-isoform VHL-HIF extrapolations remain unresolved. Pharmacological degradation adds a temporal layer: vepdegestrant acts through oestrogen receptor-α degradation, whereas its FDA-authorised companion diagnostic selects patients by plasma ESR1 genotype, and serial target measurements are required to distinguish productive target loss, failed loss, recovery and downstream escape. Protein-fate measurement may be informative if it resolves a reproducible, decision-relevant state that genotype, abundance or pathway-output markers leave ambiguous. We define the experimental and clinical evidence needed to test whether such measurements can inform precision strategies to address drug resistance and cancer progression. Conclusion remain limited to the contrastive cases and United States records reviewed through 26 July 2026, with separately dated updates to selected trial records.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1960932"},"PeriodicalIF":5.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13650186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166125","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 saliva-derived metabolic signature with multi-omics support for oral squamous cell carcinoma diagnosis.","authors":"Hongyu Zheng, Shuijuan Hu, Pingping Tian, Jing Xu, Yaqing Ma, Yuelian Liu, Kaitong Wei, Qiang Sun","doi":"10.3389/fcell.2026.1901210","DOIUrl":"https://doi.org/10.3389/fcell.2026.1901210","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) lacks practical and non-invasive biomarkers for case detection. Saliva is an attractive source for biomarker discovery; however, many reported candidates lack support from independent biological data layers.</p><p><strong>Methods: </strong>We performed untargeted salivary metabolomics in 40 patients with OSCC and 40 healthy controls. Differential metabolites were identified using multivariate and univariate analyses. Candidate diagnostic metabolites were prioritized by support vector machine-recursive feature elimination, random forest, and receiver operating characteristic (ROC) analyses. The biological context of the salivary findings was further examined using two GEO transcriptomic cohorts, the TCGA-HNSC cohort, a single-cell RNA sequencing dataset, and public protein-level resources including the Human Protein Atlas and CPTAC.</p><p><strong>Results: </strong>OSCC and control samples showed distinct salivary metabolic profiles, and 19 annotated endogenous differential metabolites were retained for downstream analysis. These alterations were mainly enriched in amino acid- and lipid-related pathways, including arginine and proline metabolism. Within the discovery cohort, internal cross-validation and feature ranking converged on a seven-metabolite panel; however, because feature selection and evaluation were performed on the same 80 samples without nested cross-validation, performance estimates are subject to optimism bias and are not reported here as validated diagnostic metrics. In GSE6631 and GSE37991 showed concordant downregulation of linoleic acid metabolism, arachidonic acid metabolism, bile acid-related programs, fatty acid metabolism, and peroxisome pathways in tumor tissue. Single-cell analysis further suggested reduced activity of curated metabolic modules in malignant cells and tumor-associated tissue states, though these comparisons did not account for patient-level dependence. At the protein level, ALDH1A1 and VDR were decreased, whereas SLC7A11 was increased in tumor tissue.</p><p><strong>Conclusion: </strong>OSCC was associated with a saliva-derived metabolic signature supported by pathway-level concordance across multiple public data layers. The overall pattern suggests lipid remodeling, reduced bile acid-related signaling, altered amino acid metabolism, and enhanced redox defense. These findings support further targeted quantification and external validation of saliva-based biomarker candidates for OSCC, while the current panel should be regarded as a preliminary discovery-set candidate signature.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1901210"},"PeriodicalIF":5.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165813","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":"PI3K/AKT/mTOR signaling at the immune checkpoint interface in lung cancer: molecular mechanisms, Tumor-Immune remodeling, therapeutic resistance, and emerging treatment strategies.","authors":"Hongliang Jin, Fan Yang, Shi Zong, Wenli Sun","doi":"10.3389/fcell.2026.1952310","DOIUrl":"https://doi.org/10.3389/fcell.2026.1952310","url":null,"abstract":"<p><p>Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have substantially improved the treatment of lung cancer, yet durable responses remain limited by primary and acquired resistance. Increasing evidence identifies the PI3K/AKT/mTOR pathway as a central link between oncogenic signaling, metabolic adaptation, and tumor immune suppression. Genetic and molecular alterations, including PIK3CA activation, PTEN loss, and aberrant EGFR or ALK signaling, can activate this pathway and regulate PD-L1 expression at transcriptional, translational, and post-translational levels. Conversely, tumor-intrinsic PD-L1 signaling can reinforce PI3K/AKT/mTOR activity, promoting proliferation, survival, glycolysis, epithelial-mesenchymal transition, and resistance to therapy. This reciprocal interaction establishes a feedforward circuit that supports lung cancer progression and immune escape. The pathway also reshapes the tumor microenvironment by promoting regulatory T-cell expansion, M2-like macrophage polarization, myeloid-cell recruitment, CD8⁺ T-cell dysfunction, and resistance to immune checkpoint blockade. This review critically examines the bidirectional crosstalk between PI3K/AKT/mTOR and PD-1/PD-L1 signaling in lung cancer and summarizes the molecular regulators that connect these pathways. We further discuss therapeutic strategies designed to disrupt this network, including PI3K, AKT, and mTOR inhibitors; targeted therapies; chemotherapy and radiotherapy combinations; antiangiogenic approaches; nanomedicine; extracellular-vesicle-based delivery; cell-based interventions; and natural compounds. Although preclinical evidence supports combining pathway inhibition with immune checkpoint blockade, clinical translation is challenged by pathway complexity, context-dependent regulation of PD-L1, systemic toxicity, and the absence of validated predictive biomarkers. Biomarker-guided patient selection, optimized dosing and sequencing, and selective targeting of tumor- or immune-cell-specific pathway components will therefore be essential for converting this mechanistic rationale into durable clinical benefit.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1952310"},"PeriodicalIF":5.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13650427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164500","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":"MAFLD and impaired bone formation in children: association with reduced serum LCAT.","authors":"Lingyan Zhu, Lin Xu, Lanshu Yang, Baolan Sun, Weixia Yang","doi":"10.3389/fcell.2026.1902360","DOIUrl":"https://doi.org/10.3389/fcell.2026.1902360","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate bone metabolism indicators and serum lecithin-cholesterol acyltransferase (LCAT) levels in children with metabolic dysfunction-associated fatty liver disease (MAFLD), and to explore their interrelationship.</p><p><strong>Patients and methods: </strong>This study enrolled 127 children aged 6-14 years, classified into control (n = 42), obesity without hepatic steatosis (n = 41), and MAFLD (n = 44) groups. All participants underwent clinical evaluation, laboratory testing, and liver ultrasonography. Serum LCAT was quantified by enzyme-linked immunosorbent assay (ELISA). Bone turnover markers, including procollagen type I N-terminal propeptide (PINP), β-C-terminal telopeptide of type I collagen (β-CTX), and 25-hydroxyvitamin D [25-(OH) D], were measured via electrochemiluminescence. Independent risk factors for impaired bone formation were analyzed using multivariable ordinal logistic regression.</p><p><strong>Results: </strong>Serum LCAT concentrations were highest in controls (58.27 ± 4.43 mg/L), followed by obesity without hepatic steatosis (46.13 ± 3.37 mg/L), and lowest in the MAFLD group (40.71 ± 3.44 mg/L) (<i>P</i> < 0.001). The proportion of children with PINP below the 25th percentile was significantly greater in the MAFLD group (88.64%) than in obesity (48.78%) and control groups (35.71%) (<i>P</i> < 0.001). Significant intergroup differences were observed for 25-(OH) D, PINP values, PINP grade, and PINP/β-CTX ratio; PINP grade distribution differed among groups (<i>P</i> < 0.001), whereas β-CTX grade did not. Spearman analysis revealed significant correlations of LCAT with HDL-C, AST, ALT, fatty liver status, 25-(OH) D, and PINP grade (all <i>P</i> < 0.001). Multivariable ordinal logistic regression identified MAFLD (<i>OR</i> = 4.74, 95% CI: 1.41-15.99, <i>P</i> = 0.012) and older age (<i>OR</i> = 1.38, 95% CI: 1.08-1.75, <i>P</i> = 0.009) as independent factors associated with lower PINP grade, whereas LCAT was not independently associated with PINP grade.</p><p><strong>Conclusion: </strong>MAFLD was independently associated with lower PINP status in children. Reduced serum LCAT levels were associated with MAFLD and unfavorable bone formation status but were not independently associated with PINP grade after multivariable adjustment. LCAT may therefore represent an associated biomarker within the liver-bone axis, requiring validation through prospective studies, formal mediation analyses, and mechanistic experiments.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1902360"},"PeriodicalIF":5.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165561","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":"Integrated lipidomic and transcriptomic profiling of imiquimod-induced psoriasiform dermatitis.","authors":"Eva Wisniewski, Wenwen Du, Jenna A Himelstein, Gergő Szanda, Taylor J Woodward, Ken Mackie, Heather B Bradshaw","doi":"10.3389/fcell.2026.1881695","DOIUrl":"https://doi.org/10.3389/fcell.2026.1881695","url":null,"abstract":"<p><p>Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and immune dysregulation. Emerging clinical and experimental evidence suggests that endogenous lipid (endolipid) signaling systems, including the endocannabinoid system (ECS), represent a promising therapeutic target to treat psoriasis; however, comprehensive characterization of small-molecule endolipids and related proteins in psoriatic skin and their relationship to systemic changes remains limited. Here, we used the imiquimod (IMQ)-induced mouse model of psoriasis to perform combined lipidomic and transcriptional profiling of endolipid signaling in both skin and plasma. Targeted lipidomics revealed a striking divergence between tissues: most endolipids increased in inflamed skin but decreased in plasma, including the canonical ECS lipids anandamide and 2-arachidonoylglycerol. In contrast, selected lipid species, including taurine-conjugated metabolites (both <i>N</i>-acyl taurines and bile acids), were elevated in both tissues, indicating pathway-specific regulation. Targeted transcriptional analysis of whole skin showed reduced expression of key endolipid biosynthetic enzymes (<i>Napepld, Dagla, Daglb</i>) and the cannabinoid receptor <i>Cnr1</i>, while <i>Cnr2</i> and ECS-related metabolic enzymes remained unchanged. Additional alterations were observed in transcripts involved in related endolipid signaling (<i>Trpv1, Trpv4, Ppara, Pparg, Gpr55</i>), bile acid metabolism (<i>Fxr, Bsep, Fabp4, Fabp5, Cyp27a1, Cyp8b1</i>), and inflammatory pathways (<i>Cox-2</i>). To resolve this apparent discrepancy between lipid levels and gene expression, we performed compartment-specific analyses of epidermal and dermal layers. These revealed a predominantly suppressive epidermal response across multiple ECS-related proteins, contrasted by a more variable dermal profile with selective preservation or upregulation, particularly of <i>Cnr2</i>. Together, these findings demonstrate that psoriasiform inflammation is associated with compartment-specific remodeling of endolipid signaling across skin and systemic compartments, underscoring the functional heterogeneity of epidermal and dermal layers. This dataset provides novel insights into the dysregulation of endolipid signaling systems in psoriasis and provides a foundation for the development of spatially informed, lipid-based therapeutic strategies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1881695"},"PeriodicalIF":5.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166109","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":"Cellular metabolomics reveals the osteogenic mechanism of MC3T3-E1 cells in porous Ti6Al4V scaffolds under low-intensity pulsed ultrasound.","authors":"Xinyun Li, Lin Wu","doi":"10.3389/fcell.2026.1945138","DOIUrl":"10.3389/fcell.2026.1945138","url":null,"abstract":"<p><strong>Introduction: </strong>Porous titanium alloy scaffolds offer multiple advantages in treating large-area bone defects; however, their poor bioactivity limits their application. Low-intensity pulsed ultrasound (LIPUS) serves as a non-invasive method to enhance bone regeneration in porous titanium-6aluminium-4vanadium (Ti6Al4V) alloy scaffolds. This study aimed to examine the biological behavior and metabolism of murine osteoblastic MC3T3-E1 cells in porous Ti6Al4V (pTi64) scaffolds under LIPUS.</p><p><strong>Methods: </strong>MC3T3-E1 cells were incubated in pTi64 scaffolds and stimulated with LIPUS. Cell morphology, viability, and osteogenic-related gene expression were evaluated <i>in vitro</i>. Intracellular metabolites of MC3T3-E1 cells incubated in pTi64 scaffolds and stimulated with LIPUS for 7 days were analyzed using an ultraperformance liquid chromatography coupled with a triple quadrupole-linear ion trap mass spectrometer (UPLC-QTRAP-MS)-based cellular metabolomics approach.</p><p><strong>Results: </strong><i>In vitro</i>, MC3T3-E1 cells in the pTi64+LIPUS group exhibited enhanced morphology, viability, and osteogenic-related gene expression compared with the pTi64 group, suggesting that LIPUS enhances cell morphology, reduces apoptosis, and promotes osteogenic differentiation in pTi64 scaffolds. LIPUS treatment altered the cellular metabolic network; 86 differential metabolites were identified. Alterations in metabolic pathways were associated with the one-carbon pool by folate, pantothenate and coenzyme A biosynthesis, as well as the metabolism of amino acids, glycerolipids, and arachidonic acid.</p><p><strong>Discussion: </strong>These findings offer novel insights into the osteogenic mechanisms of MC3T3-E1 cells in pTi64 scaffolds under LIPUS.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1945138"},"PeriodicalIF":5.3,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135754","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 role of cementoblasts in root resorption induced by orthodontic treatment: from mechanosensation to repair potential.","authors":"Yue Feng, Yanling Xie, Xing Hu, Zhiqiao Qiu, Shuixue Mo","doi":"10.3389/fcell.2026.1953825","DOIUrl":"10.3389/fcell.2026.1953825","url":null,"abstract":"<p><p>While alveolar bone has high remodeling activity under physiological conditions, cementum has a strong antiresorptive capacity. Cementoblasts are the primary functional and mechanosensitive cells on the cementum surface that maintain the structural homeostasis of the tooth root. However, excessive or sustained orthodontic force applied during treatment often induces irreversible orthodontically induced inflammatory root resorption (OIIRR), characterized by impaired cementoblast function and defective root surface repair. Although the precise molecular mechanisms underlying cementoblast dysfunction and the progression of root resorption under orthodontic force remain incompletely understood, posing major challenges for the prevention and management of OIIRR, orthodontic force-induced programmed cell death and secretory dysregulation in cementoblasts are known to hinder the self-repair of resorption lacunae, thereby exacerbating root tissue destruction. Consequently, intervention strategies-including physical therapy, pharmacological therapy, and biomaterial-based approaches-targeting the biological properties of cementoblasts are being developed to reactivate their differentiation and mineralization potential and promote functional repair of the root surface. This review provides a comprehensive overview of the biological role of cementoblasts in orthodontic root resorption and repair, establishing a theoretical basis and providing new insights for the development of cementoblast-targeted strategies to prevent and treat OIIRR.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1953825"},"PeriodicalIF":5.3,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135830","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":"Geno-guided targeting of ferroptosis: a multi-layered network to overcome radioresistance in lung cancer.","authors":"Shifang Sang, Guangchao Lv, Shiyun Feng, Hui Zhao, Yulong Ren, Dianlong Jin, Kaizhong Wang","doi":"10.3389/fcell.2026.1886712","DOIUrl":"10.3389/fcell.2026.1886712","url":null,"abstract":"<p><p>Lung cancer is one of the most prevalent and lethal malignancies worldwide, and radiotherapy serves as a standard therapeutic modality for the management of advanced or inoperable non-small cell lung cancer. However, radioresistance remains a major obstacle that compromises therapeutic efficacy and drives tumor recurrence. Ferroptosis-an iron-dependent, lipid peroxidation-governed form of regulated cell death-substantially contributes to radiation-mediated tumor cell elimination. This review establishes a multi-layered regulatory network through which ferroptosis mediates radioresistance in lung cancer, spanning genetic mutations, epigenetic and RNA-based regulation, protein post-translational modifications, and lipid metabolism reprogramming. Unlike existing reviews, this paper stratifies ferroptotic vulnerability and radiosensitivity according to common driver genotypes-including TP53, LKB1and KEAP1-and proposes a genotype-guided paradigm for precise radiosensitization. By integrating these molecular layers, review provides a supplementary theoretical framework for optimizing radiotherapy in lung cancer and highlights how targeting ferroptosis can overcome resistance in a mutation-specific manner. Furthermore, the crosstalk between ferroptosis and cuproptosis represents a promising combinatorial therapeutic avenue that warrants further preclinical and clinical investigation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1886712"},"PeriodicalIF":5.3,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135844","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":"Spatial proteomics: technical evolution and applications in cancer research.","authors":"Xiaoxiao Tian, Di Huang, Jiaxiang Hu","doi":"10.3389/fcell.2026.1914317","DOIUrl":"10.3389/fcell.2026.1914317","url":null,"abstract":"<p><p>Spatial proteomics is reshaping tissue-based cancer research by linking protein expression to cellular identity, tissue architecture and clinical behavior. Conventional proteomics has provided powerful tools for protein identification and quantification, but most bulk workflows erase the spatial relationships that define tumor ecology. In contrast, spatial proteomics combines multiplexed imaging, mass spectrometry-based tissue analysis, region-selected profiling and computational spatial statistics to measure proteins in their native tissue context. This review summarizes the development of proteomics from early separation and mass spectrometry technologies to current spatial platforms. It then focuses on cancer applications, including tumor heterogeneity, tumor microenvironment, antitumor immunity, immunotherapy response, spatial biomarkers and treatment resistance. Across these areas, spatial proteomics is most valuable when it converts descriptive tissue patterns into testable hypotheses about cell states, neighborhood interactions and therapeutic vulnerabilities. The field now needs standardized workflows, clinically anchored cohorts and functional validation to move from high-dimensional tissue maps to robust translational tools.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1914317"},"PeriodicalIF":5.3,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135798","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}