IF 6 2区生物学

Cells Pub Date : 2026-09-30 DOI: 10.3390/cells15191784

Chen Wang, Huaizhou Jin, Qijie Zhang, Yanqiu Zou, Yaosen Wang, Nicolò Maccaferri, Ali Douaki, Jianguo Feng, Denis Garoli, Shangzhong Jin

{"title":"ADAMTS3 Promotes Hepatocellular Carcinoma Cell Growth and Migration Through TGF-β:TGFBR2 Signaling.","authors":"Chen Wang, Huaizhou Jin, Qijie Zhang, Yanqiu Zou, Yaosen Wang, Nicolò Maccaferri, Ali Douaki, Jianguo Feng, Denis Garoli, Shangzhong Jin","doi":"10.3390/cells15191784","DOIUrl":"10.3390/cells15191784","url":null,"abstract":"Early diagnosis of hepatocellular carcinoma (HCC) still represents a significant challenge, particularly in the context of etiological shift toward obesity and non-viral liver disease-associated HCC. Through intersection-based analysis of independent transcriptomic datasets comprising healthy controls, individuals with obesity or NAFLD, and HCC patients with viral or non-viral etiologies, we prioritized ADAMTS3, a secreted protein, for further investigation of its functional and mechanistic relevance to HCC. ADAMTS3 was upregulated in HCC and demonstrated transcriptomic discrimination between HCC and non-HCC populations. Notably, in the validation cohort, ADAMTS3 retained discriminative capacity in clinically defined alpha-fetoprotein-negative HCC patients. Functionally, ADAMTS3 knockdown impaired cell proliferation, clonogenicity, and migration, while inducing apoptosis and cell-cycle arrest. Reintroduction of ADAMTS3 partially rescued these cellular effects. Mechanistically, ADAMTS3 promotes HCC cell growth and migration through TGF-β:TGFBR2 signaling. ADAMTS3 knockdown increased extracellular TGF-β and downstream SMAD phosphorylation. Neutralization of extracellular TGF-β alleviated growth inhibition caused by ADAMTS3 knockdown. Consistently, TGFBR2 knockdown partially restored the cell growth and migration suppressed by ADAMTS3 knockdown. We also developed a DNA origami-based SERS aptasensor targeting ADAMTS3, achieving highly sensitive detection of ADAMTS3 down to 10-12 M with strong quantitative capability (R2 = 0.914). Together, our findings support a role for ADAMTS3 in promoting HCC cell growth and migration and provide a basis for further investigation of its relevance to HCC biomarker development. The DNA origami-based SERS aptasensor provides a sensitive analytical approach for future studies of circulating or serum ADAMTS3.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191572","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}

引用次数: 0

Homoharringtonine Suppresses Prostate Cancer Progression Through Modulation of the TNF/NF-κB and MAPK Signaling Pathways. 同质三尖杉碱通过调节TNF/NF-κB和MAPK信号通路抑制前列腺癌进展

IF 6 2区生物学

Cells Pub Date : 2026-09-30 DOI: 10.3390/cells15191788

Yuzhong Chen, Sisi Huang, Dongyan Huang, Yangtao Jin, Congcong Shao, Xin Su, Rongfu Yang, Juan Jiang, Jianhui Wu

引用次数: 0

Female Reproductive System Assembloids in Health and Disease. 健康与疾病中的女性生殖系统组合。

IF 6 2区生物学

Cells Pub Date : 2026-09-30 DOI: 10.3390/cells15191792

Mete Hakan Karalök, Burcu Biltekin, Turgay Barut, Süleyman Ergün

{"title":"Female Reproductive System Assembloids in Health and Disease.","authors":"Mete Hakan Karalök, Burcu Biltekin, Turgay Barut, Süleyman Ergün","doi":"10.3390/cells15191792","DOIUrl":"10.3390/cells15191792","url":null,"abstract":"In just over a decade, in vitro modeling of the female reproductive tract has advanced from planar monolayers of immortalized cells to self-organizing epithelial organoids and, most recently, to increasingly complex multicellular and multicompartment 3D models, including assembloids that combine organoids with additional organoid modules or specialized cell lineages and demonstrate post-assembly integration and self-organization. This review concentrates deliberately on organoid, assembloid, and related multicellular 3D models rather than on reproductive physiology per se. We first establish a criterion-based framework that distinguishes organoids, assembloids, co-cultures, organ-on-chip systems, and blastoids according to assembly strategy, cellular composition, and evidence of structural and functional integration, and trace the rapid consolidation of the assembloid concept from neuroscience into reproductive biology. We then survey, organ-by-organ and with a critical eye, what these models have demonstrated in the endometrium, the ovary and follicle, the fallopian tube, and the embryo-maternal interface, together with the enabling technologies (including microfluidics, vascularization strategies, biomaterials and bioprinting, and single-cell and spatial benchmarking) and the limitations that still constrain the field. We close with emerging translational opportunities in disease modeling, drug and toxicology screening, and personalized reproductive medicine, while highlighting the requirements for physiological validation, reproducibility, standardization, and appropriate ethical and regulatory oversight.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191648","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}

引用次数: 0

Mitofusin Activation Delays Aging in Caenorhabditis elegans. 丝裂酶激活延缓秀丽隐杆线虫的衰老。

IF 6 2区生物学

Cells Pub Date : 2026-09-30 DOI: 10.3390/cells15191789

Jochen Weigele, Lihong Zhang, Jiajia Li, Elisabeth Roider, Caroline E Walton, Gerald W Dorn

{"title":"Mitofusin Activation Delays Aging in Caenorhabditis elegans.","authors":"Jochen Weigele, Lihong Zhang, Jiajia Li, Elisabeth Roider, Caroline E Walton, Gerald W Dorn","doi":"10.3390/cells15191789","DOIUrl":"10.3390/cells15191789","url":null,"abstract":"Age-linked tissue dysfunction is associated with mitochondrial degeneration manifested as organelle fragmentation and respiratory dysfunction. Efforts to mitigate downstream consequences of mitochondrial degeneration, as with ROS scavengers, have not translated to the human condition. We posit that intrinsic fusion-mediated mechanisms for mitochondrial protection modulate aspects of aging linked to mitochondrial abnormalities. In C. elegans roundworms mitochondrial fusion is mediated by the mitofusin ortholog Fuzzy Onion-1 (fzo-1). Here, the addition of a mitofusin inhibitor, MFI8, to cultures of age-synchronized C. elegans shortened worm lifespan in a concentration-dependent manner. Reciprocally, the mitofusin activators Chimera and 8015-P2 prolonged worm survival in a dose-dependent manner. The pro-survival effect of Chimera was absent in worms lacking its protein target, FZO-1, and at lower concentrations Chimera-amplified survival was further increased by absence of the mitochondrial fission protein that acts in opposition to fzo-1, DRP-1. The mitofusin activator 8015-P2, which is more potent than Chimera, exhibited greater anti-aging effects on lifespan and improved worm healthspan measured as forced swimming activity and resistance to thermal and oxidative stresses. These proof-of-concept worm studies identify aging phenotypes reciprocally related to fzo-1/mitofusin activation status. As 8015-P2 is under development for use in human neurodegenerative diseases, it might alleviate aging phenotypes evoked by mitochondrial degeneration in higher species.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191570","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}

引用次数: 0

Disrupting Mitochondrial Homeostasis via TBC1D15 Protein. 通过TBC1D15蛋白破坏线粒体稳态。

IF 6 2区生物学

Cells Pub Date : 2026-09-30 DOI: 10.3390/cells15191781

Pengfei Qiang, Yan Li, Shuang Liang, Miaomiao Jiang, Shuoye Yang, Xiwei Zhang

{"title":"Disrupting Mitochondrial Homeostasis via TBC1D15 Protein.","authors":"Pengfei Qiang, Yan Li, Shuang Liang, Miaomiao Jiang, Shuoye Yang, Xiwei Zhang","doi":"10.3390/cells15191781","DOIUrl":"10.3390/cells15191781","url":null,"abstract":"Background: Mitochondria-lysosome coupling and mitophagy are fundamental to mitochondrial homeostasis, yet the determinants governing this process remain incompletely defined. This study distinguished the regulatory modes of TBC1D15 and established its functional role as a downstream effector in mitochondria-linked autophagy.Methods: PC-12 and HeLa cells were treated with CCCP, gradient-concentrated AuNPs, and CQ, combined with siRNA-mediated PINK1 knockdown. Whole-cell, mitochondrial and lysosomal fractions were analyzed by immunoblotting.Results: Inter-organelle translocation of TBC1D15, rather than its total abundance, serves as the critical switch for mitochondria-lysosome homeostasis. CCCP induced a time-dependent biphasic change in TBC1D15 that persisted upon PINK1 knockdown, indicating regulation is not strictly PINK1-dependent. High-dose AuNPs trapped TBC1D15 on mitochondria and blocked lysosomal delivery via a PINK1-independent route. AuNPs exhibited biphasic concentration-dependent effects: low concentrations moderately upregulated TBC1D15, promoting adaptive organelle contacts, while millimolar concentrations caused pathological tethering. Subcellular fractionation and CQ intervention confirmed that defective lysosomal delivery underlies mitochondrial TBC1D15 accumulation upon AuNP challenge.Conclusions: This work establishes two distinct regulatory axes converging on TBC1D15. High-dose AuNPs can serve as a specific pharmacological blocker of TBC1D15 trafficking, offering therapeutic avenues for disorders characterized by impaired mitophagy.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191593","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}

引用次数: 0

CCDC69 Regulates Adipocyte Differentiation and Cellular Morphology in SGBS Cells-A Human Preadipocyte Cell Line. CCDC69调控人前脂肪细胞系SGBS细胞的脂肪细胞分化和细胞形态。

IF 6 2区生物学

Cells Pub Date : 2026-09-30 DOI: 10.3390/cells15191782

Takeo Iwata

{"title":"CCDC69 Regulates Adipocyte Differentiation and Cellular Morphology in SGBS Cells-A Human Preadipocyte Cell Line.","authors":"Takeo Iwata","doi":"10.3390/cells15191782","DOIUrl":"10.3390/cells15191782","url":null,"abstract":"CCDC69 was previously identified as a gene upregulated during adipogenic differentiation of human Simpson-Golabi-Behmel syndrome (SGBS) preadipocytes but not mouse 3T3-L1 preadipocytes. Here, the role of CCDC69 in adipogenesis was investigated using SGBS cells. CCDC69 expression during adipogenic differentiation was assessed by quantitative reverse transcription PCR and Western blotting. CCDC69 function was examined by adenovirus-mediated overexpression and knockdown, followed by analyses of lipid accumulation, adipocyte marker expression, cell morphology, and cytoskeletal organization. CCDC69 expression increased during adipogenesis. CCDC69 overexpression enhanced adipogenesis, as indicated by increased lipid accumulation, a higher proportion of cells containing lipid droplets, and increased expression of adipocyte marker genes and proteins. Unexpectedly, CCDC69 knockdown also enhanced adipogenesis. Time-course analysis showed that CCDC69 overexpression suppressed PPARG mRNA expression during early adipogenesis but increased its expression at later stages, whereas knockdown increased PPARG expression at later stages. CCDC69 overexpression induced a flattened cell morphology accompanied by reduced fibrillar α-tubulin structures and F-actin stress fibers, whereas knockdown increased the number of small, round cells. These findings suggest that the effects of CCDC69 on adipogenesis may vary across the differentiation process in SGBS cells and are associated with adipocyte morphology and cytoskeletal organization.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191569","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}

引用次数: 0

HSP27 Provides Stress-Adaptive Proteostasis Buffering in Glioblastoma and Is Therapeutically Vulnerable. HSP27在胶质母细胞瘤中提供应激适应性蛋白酶抑制缓冲，并且在治疗上是脆弱的。

IF 6 2区生物学

Cells Pub Date : 2026-09-30 DOI: 10.3390/cells15191794

Yuexia Jiao, Qi Liu, Yuchun Zhang, Xiuyuan Wang, Xinjun Liang, Shaozhong Wei, Zijian Tang

{"title":"HSP27 Provides Stress-Adaptive Proteostasis Buffering in Glioblastoma and Is Therapeutically Vulnerable.","authors":"Yuexia Jiao, Qi Liu, Yuchun Zhang, Xiuyuan Wang, Xinjun Liang, Shaozhong Wei, Zijian Tang","doi":"10.3390/cells15191794","DOIUrl":"10.3390/cells15191794","url":null,"abstract":"Glioblastoma, isocitrate dehydrogenase (IDH)-wildtype (GBM), remains one of the most aggressive primary brain tumors, and its proteostasis machinery represents a potential therapeutic target. Here we identify HSP27 as a key regulator-associated proteostasis in glioblastoma, IDH-wildtype, where it is linked to protein synthesis, folding, stress-granule dynamics and ubiquitin-mediated turnover. Ribo-seq showed HSP27 depletion reduced global protein synthesis, while TME labeling coupled to mass spectrometry revealed increased accumulation of unfolded proteins, indicating proteotoxic stress. Proteomic analysis of isolated stress granules (SGs) revealed enhanced sequestration of translational regulators, including EIF4E, mTOR, EIF3M and QKI, into stress granules (SGs), thereby reinforcing translational repression. Ubiquitinome profiling further revealed increased ubiquitination and proteasome-dependent loss of oncogenic and translational regulators, including AKT2, PARP1, EIF4G1, EIF4A3, and DDX5. Functionally, targeting HSP27 inhibits tumor growth and sensitizes glioblastoma to translational blockade. In orthotopic models, antisense oligonucleotide targeting HSP27 in combination with Didemnin B suppressed tumor progression and prolonged survival compared with either single agent. These findings associate HSP27 with proteostasis in glioblastoma, IDH-wildtype, and suggest HSP27-dependent proteostasis buffering as a therapeutic vulnerability.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191534","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}

引用次数: 0

From Amyloid Exposure to Genetic Causality: Converging hiPSC-Based Models of Alzheimer's Disease. 从淀粉样蛋白暴露到遗传因果关系：基于hipsc的阿尔茨海默病趋同模型。

IF 6 2区生物学

Cells Pub Date : 2026-09-30 DOI: 10.3390/cells15191793

Fiorella Colasuonno, Alessio Valenza, Federica Rossin, Sandra Moreno

{"title":"From Amyloid Exposure to Genetic Causality: Converging hiPSC-Based Models of Alzheimer's Disease.","authors":"Fiorella Colasuonno, Alessio Valenza, Federica Rossin, Sandra Moreno","doi":"10.3390/cells15191793","DOIUrl":"10.3390/cells15191793","url":null,"abstract":"Alzheimer's disease (AD) is a neurodegenerative disorder in which genetic susceptibility, aging, protein aggregation, and neuroglial dysfunction converge to drive progressive neuronal loss. Although animal models and conventional cell systems have provided fundamental insights into pathomechanisms, they only partially reproduce the human-specific and multifactorial nature of AD. Human induced pluripotent stem cell (hiPSC)-based models have emerged as a powerful platform to investigate disease-relevant processes within a patient-specific genetic background while enabling the generation of multiple neural cell types and multicellular systems. In this review, we present the evolution of hiPSC-based AD modeling, from reductionist paradigms based on exogenous amyloid-β exposure to CRISPR-engineered isogenic models addressing causal mutations and genetic risk variants associated with either familial or sporadic forms. We examine the contribution of three-dimensional brain organoids and neuroglial co-culture systems in recapitulating cell-cell interactions, neuroinflammatory responses, and tissue-level pathological processes. We focus on current challenges, including the limited representation of neuronal aging, variability among organoids, and the need for standardized protocols. Finally, we discuss the translational potential of hiPSC-derived systems for target identification, drug discovery, and regenerative medicine. Collectively, these advances position hiPSC-based platforms as essential complementary models for elucidating AD pathogenesis and accelerating the development of precision therapeutic strategies.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191624","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}

引用次数: 0

Comparative Evaluation of Freezing Protocols and Cryopreservation Media for the Preservation of Alginate Encapsulated HepaRG Cells. 海藻酸盐包封HepaRG细胞冷冻方案和冷冻保存介质的比较评价。

IF 6 2区生物学

Cells Pub Date : 2026-09-30 DOI: 10.3390/cells15191783

Carla Meschini, Andrea Bartolucci, Ulysse Pereira

{"title":"Comparative Evaluation of Freezing Protocols and Cryopreservation Media for the Preservation of Alginate Encapsulated HepaRG Cells.","authors":"Carla Meschini, Andrea Bartolucci, Ulysse Pereira","doi":"10.3390/cells15191783","DOIUrl":"10.3390/cells15191783","url":null,"abstract":"Reliable storage and distribution are important for developing ready-to-use encapsulated cell products for transplantation and bioartificial liver applications. This study evaluated the cryopreservation of alginate-encapsulated HepaRG cells using a programmable controlled-rate freezing (CRF) protocol at -0.3 °C/min or conventional passive cooling at approximately -1 °C/min. Five media were tested: four commercial xeno-free formulations, including two DMSO-containing and two DMSO-free media, and a conventional formulation containing 90% fetal bovine serum and 10% DMSO. Following thawing and a 3-day recovery period, metabolic activity, albumin secretion, ammonia and lactate clearance, and phase I and phase II biotransformation activities were assessed. Cryopreservation reduced metabolic activity relative to non-frozen controls, but key hepatic functions remained detectable. The tested CRF protocol generally yielded equal or higher functional values than conventional freezing. Medium performance varied according to the endpoint assessed. Within CRF, CryoStor CS10 produced relatively high mean PrestoBlue and albumin secretion values, whereas Cellvation produced the highest mean CYP1A1/1A2 activity. These product-specific observations do not establish a general effect of DMSO. The findings support the short-term feasibility of the tested CRF protocol for this encapsulated HepaRG model but not broader clinical or drug-testing applications.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191501","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}

引用次数: 0

The Crosstalk Between Metabolic Reprogramming and Histone Methylation in Tumor Immunity and Immunotherapy. 肿瘤免疫和免疫治疗中代谢重编程和组蛋白甲基化的串扰。

IF 6 2区生物学

Cells Pub Date : 2026-09-30 DOI: 10.3390/cells15191786

Jiayao Dou, Ruicheng Xue, Wei Gao, Fan Liang

{"title":"The Crosstalk Between Metabolic Reprogramming and Histone Methylation in Tumor Immunity and Immunotherapy.","authors":"Jiayao Dou, Ruicheng Xue, Wei Gao, Fan Liang","doi":"10.3390/cells15191786","DOIUrl":"10.3390/cells15191786","url":null,"abstract":"Histone methylation regulates chromatin structure and gene expression, whereas tumor metabolism provides bioenergetic and biosynthetic inputs. These processes are bidirectionally linked: S-adenosylmethionine supplies methyl groups for histone methyltransferases, α-ketoglutarate(α-KG) supports JmjC-domain demethylases, and D-2-hydroxyglutarate (D-2HG) can inhibit α-KG-dependent dioxygenases. Conversely, histone methylation can regulate metabolic gene expression, as illustrated by KMT2D-dependent enhancer remodeling and glycolytic gene expression in melanoma models. Lactate regulates chromatin through histone lactylation, a modification distinct from histone methylation; where the two intersect, as in the retinoblastoma H3K18la-SUZ12/PRC2-H3K27me3 circuit, the crosstalk is model-specific. This review examines these interactions in tumor cells and the immune microenvironment, emphasizing enzyme specificity, histone mark, cell type and experimental context. We highlight that changes in S-adenosylmethionine or α-KG do not produce uniform effects across enzymes, loci or cell states, and that tumor-associated macrophages are not captured by a fixed M1/M2 metabolic dichotomy. Mechanistic findings, preclinical results and early-phase clinical observations are considered separately; single-arm activity reported for valemetostat in adult T-cell leukemia/lymphoma is presented as activity in a defined cohort, not as an established survival benefit. Finally, we discuss how single-cell and spatial approaches can help resolve cell-type-specific and niche-specific interactions in heterogeneous tumors.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191669","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}

引用次数: 0

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