Molecular Biology of the Cell最新文献_第3页

Mga2-mediated transcription supports mitotic nuclear expansion under lipid saturation conditions in stearoyl-CoA desaturase Ole1 mutant. 脂酰辅酶a去饱和酶Ole1突变体在脂质饱和条件下，mga2介导的转录支持核分裂扩增。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-10-08 DOI: 10.1091/mbc.E25-05-0207

You-Liang Cheng, Jung-En Kuan, Chao-Wen Wang, Rey-Huei Chen

{"title":"Mga2-mediated transcription supports mitotic nuclear expansion under lipid saturation conditions in stearoyl-CoA desaturase Ole1 mutant.","authors":"You-Liang Cheng, Jung-En Kuan, Chao-Wen Wang, Rey-Huei Chen","doi":"10.1091/mbc.E25-05-0207","DOIUrl":"https://doi.org/10.1091/mbc.E25-05-0207","url":null,"abstract":"Membrane organelles are dynamic structures that depend on fluid membranes for their integrity and function, with the fluidity primarily derived from loosely packed unsaturated lipids. We investigated how cells respond to lipid saturation and its effect on nuclear dynamics in the budding yeast Saccharomyces cerevisiae. We found that the lipid desaturase mutant ole1-20 upregulates various genes, including OLE1, primarily through the lipid saturation-sensing transcription factor Mga2. The ole1-20 mutant displays prolonged anaphase and impaired nuclear membrane expansion, which can be rescued by the membrane fluidizer glycerol and by enhanced glycerophospholipid synthesis. However, deleting MGA2 or inhibiting de novo glycerophospholipid synthesis exacerbates mitotic phenotypes in ole1-20, leading to mitotic spindle bending, unequal nuclear division, and transient nuclear leakage. Our study underscores the importance of lipid unsaturation in nuclear dynamics during mitosis and highlights the crucial role of Mga2-mediated gene regulation in maintaining glycerophospholipid homeostasis necessary for proper nuclear membrane expansion and division in response to lipid saturation. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"mbcE25050207"},"PeriodicalIF":2.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Structured Framework of Cytoskeletal Proteins and Non-centrosomal Microtubules Promote the Initiation and Elongation of Invadopodia. 细胞骨架蛋白和非中心体微管的结构框架促进Invadopodia的起始和延伸。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-10-08 DOI: 10.1091/mbc.E25-07-0313

Mark Garewal, Pedro Ramos, Kenneth A Myers

引用次数: 0

Endosome maturation during ER stress relies on the ubiquitin-binding domain of histone deacetylase 6. 内质网应激期间内核体的成熟依赖于组蛋白去乙酰化酶6的泛素结合域。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-10-01 Epub Date: 2025-08-13 DOI: 10.1091/mbc.E25-01-0024

Katherine M Piscopo, Brooke Larson, Anna M Christiansen, Jason M Perry, Julie Hollien

{"title":"Endosome maturation during ER stress relies on the ubiquitin-binding domain of histone deacetylase 6.","authors":"Katherine M Piscopo, Brooke Larson, Anna M Christiansen, Jason M Perry, Julie Hollien","doi":"10.1091/mbc.E25-01-0024","DOIUrl":"10.1091/mbc.E25-01-0024","url":null,"abstract":"Histone deacetylase 6 (HDAC6) helps cells manage misfolded proteins by transporting ubiquitin (UB)-associated structures toward the microtubule organizing center, where they can be sequestered and degraded by lysosomes. Here, we show that when cells are subjected to acute protein-folding stress in the endoplasmic reticulum (ER), HDAC6 depletion results in the appearance of enlarged endosomes that are highly decorated with UB and colocalize with both early and late endosome markers. The C-terminal UB-binding domain and adjacent disordered regions of HDAC6 are necessary and sufficient to rescue this endosomal phenotype in cells lacking endogenous HDAC6. HDAC6 deficiency does not appear to prevent the recruitment of endosomal sorting complexes required for transport (ESCRT), which coordinate endosome maturation. However, overexpression of HDAC6 can reverse endosome phenotypes associated with the depletion of the early ESCRT factor HRS. We speculate that HDAC6 facilitates the packaging and processing of endosomal cargo when the endomembrane system is under stress.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar120"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Genetic dissection of the Drosophila BLOC-1 complex reveals distinctions in synaptic localization and homeostatic plasticity. 果蝇block -1复合物的遗传解剖揭示了突触定位和稳态可塑性的区别。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-10-01 Epub Date: 2025-08-13 DOI: 10.1091/mbc.E24-09-0392

Rebecca Stark, Caleb Dehn, Neelia Abadi, Yu Xiong, Landon Porter, Xun Chen, Dion Dickman

{"title":"Genetic dissection of the Drosophila BLOC-1 complex reveals distinctions in synaptic localization and homeostatic plasticity.","authors":"Rebecca Stark, Caleb Dehn, Neelia Abadi, Yu Xiong, Landon Porter, Xun Chen, Dion Dickman","doi":"10.1091/mbc.E24-09-0392","DOIUrl":"10.1091/mbc.E24-09-0392","url":null,"abstract":"Neuronal trafficking pathways must operate with high fidelity and speed, adapting to the dynamic demands of synaptic activity to maintain stable functionality. The biogenesis of lysosome-related organelles complex 1 (BLOC-1) is an attractive candidate to stabilize synaptic function during such challenges. BLOC-1 is an evolutionarily conserved protein complex composed of eight subunits involved in vesicle trafficking. In the nervous system, the BLOC-1 is associated with neurodevelopmental diseases and synaptic plasticity. However, the functions of each BLOC-1 component remain enigmatic. Here, we use CRISPR to mutate each Drosophila BLOC-1 gene to investigate roles in synaptic growth, function, and homeostatic plasticity. First, we show that BLOC-1 mutations are viable, with no defects in synaptic growth, morphology, or baseline function. We then demonstrate distinct synaptic localization patterns of BLOC-1 components. Finally, we show that only two of the eight BLOC-1 components, dysbindin and snapin, are necessary for presynaptic homeostatic potentiation. These results indicate separable functions and distinct synaptic localization patterns of BLOC-1 subunits, and a need to reconsider predictions made from biochemical models of BLOC-1.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"br23"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Mitochondrial dysfunction and lipid dysregulation in yeast lacking phosphatidylserine. 缺乏磷脂酰丝氨酸的酵母线粒体功能障碍和脂质失调。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-10-01 Epub Date: 2025-08-13 DOI: 10.1091/mbc.E25-03-0128

Alaumy Joshi, Zakery N Baker, Rachel A Stanfield, Dimitris T Kalafatis, David J Pagliarini, Vishal M Gohil

{"title":"Mitochondrial dysfunction and lipid dysregulation in yeast lacking phosphatidylserine.","authors":"Alaumy Joshi, Zakery N Baker, Rachel A Stanfield, Dimitris T Kalafatis, David J Pagliarini, Vishal M Gohil","doi":"10.1091/mbc.E25-03-0128","DOIUrl":"10.1091/mbc.E25-03-0128","url":null,"abstract":"Mitochondrial membrane phospholipids impact mitochondrial structure and function by influencing the assembly and activity of membrane proteins. Although the specific roles of the three most abundant mitochondrial phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL), have been extensively studied, the precise function of less abundant phosphatidylserine (PS) is not yet determined. Here, we used genetic and nutritional manipulation to engineer a set of yeast mutants, including a mutant completely devoid of PS, to assess its role in mitochondrial bioenergetics and lipid homeostasis. To circumvent the confounding effect of downstream PS products, PE and PC, we exogenously supplied ethanolamine that allows their biosynthesis via an alternate pathway. Using this system, we demonstrate that PS does not impact the abundance or the assembly of mitochondrial respiratory chain complexes; however, mitochondrial respiration is impaired. PS-lacking mitochondria cannot maintain mitochondrial membrane potential and exhibit leaky membranes. A mass spectrometry-based analysis of the cellular and mitochondrial lipidomes revealed an unexpected increase in odd-chain fatty acid-containing lipids in PS-lacking cells that may impact mitochondrial bioenergetics. Our study uncovers novel roles of PS in mitochondrial membrane biogenesis and bioenergetics and provides a viable eukaryotic system to unravel the cellular functions of PS.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar121"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Cross-talk between Rac and Rap GTPases in migrating cells. 迁移细胞中Rac和Rap gtp酶间的串扰。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-10-01 Epub Date: 2025-08-06 DOI: 10.1091/mbc.E25-02-0058

Ricarda Lüttig, Suchet Nanda, Haritha T Chandran, Leif Dehmelt

{"title":"Cross-talk between Rac and Rap GTPases in migrating cells.","authors":"Ricarda Lüttig, Suchet Nanda, Haritha T Chandran, Leif Dehmelt","doi":"10.1091/mbc.E25-02-0058","DOIUrl":"10.1091/mbc.E25-02-0058","url":null,"abstract":"To enable effective cell migration, local cell protrusion has to be coordinated with local cell attachment. Here, we investigate spatiotemporal activity patterns of key regulators of cell protrusion and adhesion, the small GTPases Rac and Rap, in migrating cells. These analyses show that Rac activity correlates very tightly with instantaneous cell protrusion events, while the Rap activity stays elevated for prolonged time periods after protrusion and is also detectable before cell protrusion. Direct analysis of activity cross-talk in living cells via light-based perturbation methods revealed that Rap can efficiently activate Rac; however, reciprocal cross-talk from Rac to Rap was not detectable. These findings suggest that Rap plays an instructive role in the generation of cell protrusions by its ability to activate Rac. Furthermore, prolonged Rap activity suggests that this molecule also plays a role in maintenance or stabilization of cell protrusions. Indeed, analysis of Rap1-depleted A431 cells revealed a significant reduction of cell attachment, suggesting that Rap-stimulated cell adhesion can stabilize newly formed protrusions. Taken together, our study suggests a mechanism, by which cell protrusion is coupled to cell adhesion via unidirectional cross-talk that connects the activity of the small GTPases Rap and Rac.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar119"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

A growing problem: The many unsolved mysteries of cell growth. 一个日益严重的问题：细胞生长的许多未解之谜。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-10-01 Epub Date: 2025-08-13 DOI: 10.1091/mbc.E21-07-0359

Douglas R Kellogg

{"title":"A growing problem: The many unsolved mysteries of cell growth.","authors":"Douglas R Kellogg","doi":"10.1091/mbc.E21-07-0359","DOIUrl":"10.1091/mbc.E21-07-0359","url":null,"abstract":"Growth is the essential vital process that drives life forward and always occurs within cells. Cell growth fuels the cell divisions that drive proliferation of single-celled organisms and growth of multicellular organisms. Mechanisms that control the extent and location of growth within cells generate the extraordinary diversity of cell sizes and shapes seen across the tree of life and within the human body, and nearly all cancers show profound defects in control of cell growth that lead to severe aberrations in cell size and shape. Yet we know little about how cell growth occurs or how it is controlled. For decades we have known how basic building blocks such as amino acids and lipids are built, but an enormous gap has always remained in our understanding of how these building blocks are used to build out cells of highly diverse sizes and shapes under varying environmental conditions and in diverse developmental contexts. Given the fundamental importance of growth in biology and cancer, our minimal understanding of cell growth is a growing problem. Here, a few of the intriguing and important questions about cell growth are considered.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"pe8"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

SynapseNet: Deep learning for automatic synapse reconstruction. SynapseNet：自动突触重建的深度学习。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-10-01 Epub Date: 2025-08-28 DOI: 10.1091/mbc.E24-11-0519

Sarah Muth, Frederieke Moschref, Luca Freckmann, Sophia Mutschall, Ines Hojas-Garcia-Plaza, Julius N Bahr, Arsen Petrovic, Thanh Thao Do, Valentin Schwarze, Anwai Archit, Kirsten Weyand, Susann Michanski, Lydia Maus, Cordelia Imig, Anika Hintze, Nils Brose, Carolin Wichmann, Ruben Fernandez-Busnadiego, Tobias Moser, Silvio O Rizzoli, Benjamin H Cooper, Constantin Pape

{"title":"SynapseNet: Deep learning for automatic synapse reconstruction.","authors":"Sarah Muth, Frederieke Moschref, Luca Freckmann, Sophia Mutschall, Ines Hojas-Garcia-Plaza, Julius N Bahr, Arsen Petrovic, Thanh Thao Do, Valentin Schwarze, Anwai Archit, Kirsten Weyand, Susann Michanski, Lydia Maus, Cordelia Imig, Anika Hintze, Nils Brose, Carolin Wichmann, Ruben Fernandez-Busnadiego, Tobias Moser, Silvio O Rizzoli, Benjamin H Cooper, Constantin Pape","doi":"10.1091/mbc.E24-11-0519","DOIUrl":"10.1091/mbc.E24-11-0519","url":null,"abstract":"Electron microscopy is an important technique for the study of synaptic morphology and its relation to synaptic function. The data analysis for this task requires the segmentation of the relevant synaptic structures, such as synaptic vesicles (SV), active zones, mitochondria, presynaptic densities, synaptic ribbons, and synaptic compartments. Previous studies were predominantly based on manual segmentation, which is very time-consuming and prevented the systematic analysis of large datasets. Here, we introduce SynapseNet, a tool for the automatic segmentation and analysis of synapses in electron micrographs. It can reliably segment SVs and other synaptic structures in a wide range of electron microscopy approaches, thanks to a large annotated dataset, which we assembled, and domain adaptation functionality we developed. We demonstrated its capability for (semi-)automatic biological analysis in two applications and made it available as an easy-to-use tool to enable novel data-driven insights into synapse organization and function.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar127"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 hereditary spastic paraplegia type 21 (SPG21) protein is a RAB7A effector that promotes noncanonical mTORC1-catalyzed TFEB phosphorylation and cytoplasmic retention. 遗传性痉挛性截瘫21型（SPG21）蛋白是一种RAB7A效应蛋白，可促进mtorc1催化的TFEB磷酸化和细胞质保留。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-10-01 Epub Date: 2025-08-20 DOI: 10.1091/mbc.E25-07-0346

Jennifer M Kunselman, Chad D Williamson, Adriana E Golding, Rui Jia, Mira Sohn, Ryan K Dale, Juan S Bonifacino

{"title":"The hereditary spastic paraplegia type 21 (SPG21) protein is a RAB7A effector that promotes noncanonical mTORC1-catalyzed TFEB phosphorylation and cytoplasmic retention.","authors":"Jennifer M Kunselman, Chad D Williamson, Adriana E Golding, Rui Jia, Mira Sohn, Ryan K Dale, Juan S Bonifacino","doi":"10.1091/mbc.E25-07-0346","DOIUrl":"10.1091/mbc.E25-07-0346","url":null,"abstract":"Hereditary spastic paraplegia type 21 (SPG21) is an inherited neurological disorder caused by biallelic mutations in the SPG21 gene, which encodes a protein named SPG21 or maspardin. Herein, we report that the SPG21 protein localizes to endolysosomes through interaction with the GTP-bound form of RAB7A. Disease-associated SPG21 variants reduce expression of SPG21 and disrupt its endolysosomal localization in both nonneuronal cells and neurons. Consistent with this localization, functional dependency analysis links SPG21 to endolysosomal and mTORC1 signaling pathways. Biochemical studies reveal that SPG21 depletion does not affect phosphorylation of canonical mTORC1 substrates such as ULK1, S6K1, 4E-BP1, but reduces phosphorylation of the noncanonical mTORC1 substrate TFEB. This enhances nuclear localization of TFEB and expression of a subset of TFEB-target genes. We conclude that SPG21 acts as a RAB7A effector that promotes noncanonical mTORC1-catalyzed phosphorylation of TFEB, thereby suppressing its nuclear localization and transcriptional activity. These findings link SPG21 dysfunction to altered endolysosomal signaling, offering new insights into SPG21 pathogenesis.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar123"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

TGFβ1-TNFα-regulated secretion of neutrophil chemokines is independent of epithelial-mesenchymal transition in breast tumor cells. tgf - β1- tnf - α调节中性粒细胞趋化因子的分泌，不依赖于乳腺肿瘤细胞上皮-间质转化。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-10-01 Epub Date: 2025-08-20 DOI: 10.1091/mbc.E25-07-0340

Shuvasree SenGupta, Erez Cohen, Joseph Serrenho, Kaleb Ott, Pierre A Coulombe, Carole A Parent

{"title":"TGFβ1-TNFα-regulated secretion of neutrophil chemokines is independent of epithelial-mesenchymal transition in breast tumor cells.","authors":"Shuvasree SenGupta, Erez Cohen, Joseph Serrenho, Kaleb Ott, Pierre A Coulombe, Carole A Parent","doi":"10.1091/mbc.E25-07-0340","DOIUrl":"10.1091/mbc.E25-07-0340","url":null,"abstract":"Neutrophils exert tumor-promoting roles in breast cancer and are particularly prominent in aggressive breast tumors. The proinflammatory signals TGF-β1 and TNF-α are upregulated in breast tumors and induce epithelial-to-mesenchymal transitions (EMT), a process linked to cancer cell aggressiveness. Here, we investigated the roles of TGF-β1 and TNF-α in the recruitment of neutrophils by breast cancer cells. Dual-treatment with TGF-β1 and TNF-α induces EMT signatures in premalignant M2 cells, which are part of the MCF10A breast cancer progression model. Conditioned media (CM) harvested from M2 cells treated with TGF-β1/TNF-α gives rise to amplified neutrophil chemotaxis compared with CM from vehicle-treated M2 cells. This response correlates with higher levels of the neutrophil chemokines CXCL1 and CXCL8, in a p38MAPK-dependent manner, and is attenuated by CXCL8-neutralizing antibodies. We combined gene editing, immunological, and biochemical assays to show that neutrophil recruitment and EMT are uncoupled in treated M2 cells. Finally, analysis of transcriptomic databases of cancer cell lines revealed a significant correlation between CXCL8 and TGF-β1/TNF-α-regulated or effector genes in breast cancer. These findings establish a novel role for the TGF-β1/TNF-α/p38 MAPK signaling axis in regulating neutrophil recruitment in breast cancer, independent of their profound impact on EMT.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar122"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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