Molecular Biology of the Cell最新文献_第7页

Image-based discrimination of the early stages of mesenchymal stem cell differentiation. 基于图像辨别间充质干细胞分化的早期阶段。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 Epub Date: 2024-06-05 DOI: 10.1091/mbc.E24-02-0095

Justin Hoffman, Shiyuan Zheng, Huaiying Zhang, Robert F Murphy, Kris Noel Dahl

{"title":"Image-based discrimination of the early stages of mesenchymal stem cell differentiation.","authors":"Justin Hoffman, Shiyuan Zheng, Huaiying Zhang, Robert F Murphy, Kris Noel Dahl","doi":"10.1091/mbc.E24-02-0095","DOIUrl":"10.1091/mbc.E24-02-0095","url":null,"abstract":"Mesenchymal stem cells (MSCs) are self-renewing, multipotent cells, which can be used in cellular and tissue therapeutics. MSCs cell number can be expanded in vitro, but premature differentiation results in reduced cell number and compromised therapeutic efficacies. Current techniques fail to discriminate the \"stem-like\" population from early stages (12 h) of differentiated MSC population. Here, we imaged nuclear structure and actin architecture using immunofluorescence and used deep learning-based computer vision technology to discriminate the early stages (6-12 h) of MSC differentiation. Convolutional neural network models trained by nucleus and actin images have high accuracy in reporting MSC differentiation; nuclear images alone can identify early stages of differentiation. Concurrently, we show that chromatin fluidity and heterochromatin levels or localization change during early MSC differentiation. This study quantifies changes in cell architecture during early MSC differentiation and describes a novel image-based diagnostic tool that could be widely used in MSC culture, expansion and utilization.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262024","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

Maximizing Access to Cell Biology for PEERS: Retracting the term minority in favor of a more inclusive lexicon. 最大限度地为 PEERS 提供细胞生物学知识：收回 "少数群体 "一词，使用更具包容性的词汇。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 DOI: 10.1091/mbc.E24-04-0156

Fernando Vonhoff, Dana-Lynn Ko'omoa-Lange, Jamaine S Davis, Christina M Termini, Michelle M Martínez-Montemayor

{"title":"Maximizing Access to Cell Biology for PEERS: Retracting the term minority in favor of a more inclusive lexicon.","authors":"Fernando Vonhoff, Dana-Lynn Ko'omoa-Lange, Jamaine S Davis, Christina M Termini, Michelle M Martínez-Montemayor","doi":"10.1091/mbc.E24-04-0156","DOIUrl":"10.1091/mbc.E24-04-0156","url":null,"abstract":"The word minority, when used incorrectly, is a condescending term that segregates, inaccurately represents groups as being smaller or less important, and fuels microaggressions. Scientific societies and other institutions have normalized using the word minority, or the \"M word,\" to refer to members of underrepresented groups in Science, Technology, Engineering, and Mathematics (STEM). The message put forth using the term minority often directly conflicts with the inclusive agenda these societies seek to enact. More inclusive acronyms such as PEER (Persons Excluded because of their Ethnicity or Race) have been created to more accurately reflect the active process of exclusion by institutions. Here, we detail the rationale behind the decision to eradicate the word minority from the name of a prominent committee within the American Society for Cell Biology (ASCB). The ASCB Minority Affairs Committee changed its name to the Maximizing Access to Cell Biology for PEERS Committee. Herein, we emphasize the basis for the name change and highlight the contradictions intrinsic to the word minority in this context. We highlight why swift action is required for this rewording within the context of a committee dedicated to supporting the inclusion of PEERs in the scientific community.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590772","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

TFG regulates inner COPII coat recruitment to facilitate anterograde secretory protein transport. TFG 可调节 COPII 内膜的募集，从而促进分泌蛋白的前向运输。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 Epub Date: 2024-07-10 DOI: 10.1091/mbc.E24-06-0282

William Kasberg, Peter Luong, Kayla Minushkin, Iryna Pustova, Kevin A Swift, Meixian Zhao, Anjon Audhya

{"title":"TFG regulates inner COPII coat recruitment to facilitate anterograde secretory protein transport.","authors":"William Kasberg, Peter Luong, Kayla Minushkin, Iryna Pustova, Kevin A Swift, Meixian Zhao, Anjon Audhya","doi":"10.1091/mbc.E24-06-0282","DOIUrl":"10.1091/mbc.E24-06-0282","url":null,"abstract":"Coat protein complex II (COPII) governs the initial steps of biosynthetic secretory protein transport from the endoplasmic reticulum (ER), facilitating the movement of a wide variety of cargoes. Here, we demonstrate that Trk-fused gene (TFG) regulates the rate at which inner COPII coat proteins are concentrated at ER subdomains. Specifically, in cells lacking TFG, the GTPase-activating protein (GAP) Sec23 accumulates more rapidly at budding sites on the ER as compared with control cells, potentially altering the normal timing of GTP hydrolysis on Sar1. Under these conditions, anterograde trafficking of several secretory cargoes is delayed, irrespective of their predicted size. We propose that TFG controls the local, freely available pool of Sec23 during COPII coat formation and limits its capacity to prematurely destabilize COPII complexes on the ER. This function of TFG enables it to act akin to a rheostat, promoting the ordered recruitment of Sec23, which is critical for efficient secretory cargo export.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580244","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

Pulmonary matrix-derived hydrogels from patients with idiopathic pulmonary fibrosis induce a proinflammatory state in lung fibroblasts in vitro. 特发性肺纤维化患者肺基质衍生水凝胶诱导体外肺成纤维细胞的促炎状态

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 Epub Date: 2024-07-10 DOI: 10.1091/mbc.E23-11-0428

Jorge G Fernandez Davila, Amit K Singh, Durwood W Moore, Joseph Kim, Jawad A Khan, Merte Lemma, Christopher S King, Steven D Nathan, Luis R Rodriguez, Geraldine M Grant, Jeffrey L Moran

{"title":"Pulmonary matrix-derived hydrogels from patients with idiopathic pulmonary fibrosis induce a proinflammatory state in lung fibroblasts in vitro.","authors":"Jorge G Fernandez Davila, Amit K Singh, Durwood W Moore, Joseph Kim, Jawad A Khan, Merte Lemma, Christopher S King, Steven D Nathan, Luis R Rodriguez, Geraldine M Grant, Jeffrey L Moran","doi":"10.1091/mbc.E23-11-0428","DOIUrl":"10.1091/mbc.E23-11-0428","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF), one of the most common forms of interstitial lung disease, is a poorly understood, chronic, and often fatal fibroproliferative condition with only two FDA-approved medications. Understanding the pathobiology of the fibroblast in IPF is critical to evaluating and discovering novel therapeutics. Using a decellularized lung matrix derived from patients with IPF, we generate three-dimensional hydrogels as in vitro models of lung physiology and characterize the phenotype of fibroblasts seeded into the hydrogels. When cultured in IPF extracellular matrix hydrogels, IPF fibroblasts display differential contractility compared with their normal counterparts, lose the classical myofibroblast marker α-smooth muscle actin, and increase expression of proinflammatory cytokines compared with fibroblasts seeded two-dimensionally on tissue culture dishes. We validate this proinflammatory state in fibroblast-conditioned media studies with monocytes and monocyte-derived macrophages. These findings add to a growing understanding of the lung microenvironment effect on fibroblast phenotypes, shed light on the potential role of fibroblasts as immune signaling hubs during lung fibrosis, and suggest intervention in fibroblast-immune cell cross-talk as a possible novel therapeutic avenue.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580242","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

Unveiling epithelial plasticity regulation in lung cancer: Exploring the cross-talk among Tks4 scaffold protein partners. 揭示肺癌上皮细胞可塑性调控：探索 Tks4 支架蛋白伙伴间的相互关系。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 Epub Date: 2024-07-10 DOI: 10.1091/mbc.E24-03-0103

Loretta László, Anita Kurilla, Álmos Tilajka, Rita Pancsa, Tamás Takács, Julianna Novák, László Buday, Virag Vas

{"title":"Unveiling epithelial plasticity regulation in lung cancer: Exploring the cross-talk among Tks4 scaffold protein partners.","authors":"Loretta László, Anita Kurilla, Álmos Tilajka, Rita Pancsa, Tamás Takács, Julianna Novák, László Buday, Virag Vas","doi":"10.1091/mbc.E24-03-0103","DOIUrl":"10.1091/mbc.E24-03-0103","url":null,"abstract":"The epithelial-to-mesenchymal transition (EMT) represents a hallmark event in the evolution of lung cancer. This work aims to study a recently described EMT-regulating protein, Tks4, and to explore its potential as a prognostic biomarker in non-small cell lung cancer. In this study, we used CRISPR/Cas9 method to knockout (KO) Tks4 to study its functional roles in invadopodia formation, migration, and regulation of EMT marker expressions and we identified Tks4-interacting proteins. Tks4-KO A549 cells exhibited an EMT-like phenotype characterized by elongated morphology and increased expression of EMT markers. Furthermore, analyses of a large-scale lung cancer database and a patient-derived tissue array data revealed that the Tks4 mRNA level was decreased in more aggressive lung cancer stages. To understand the regulatory role of Tks4 in lung cancer, we performed a Tks4-interactome analysis via Tks4 immunoprecipitation-mass spectrometry on five different cell lines and identified CAPZA1 as a novel Tks4 partner protein. Thus, we propose that the absence of Tks4 leads to disruption of a connectome of multiple proteins and that the resulting undocking and likely mislocalization of signaling molecules impairs actin cytoskeleton rearrangement and activates EMT-like cell fate switches, both of which likely influence disease severity.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580247","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 RNA-binding protein Nab2 regulates levels of the RhoGEF Trio to govern axon and dendrite morphology. RNA 结合蛋白 Nab2 可调节 RhoGEF Trio 的水平，从而控制轴突和树突的形态。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 Epub Date: 2024-07-10 DOI: 10.1091/mbc.E24-04-0150

Carly L Lancaster, Pranav S Yalamanchili, Jordan N Goldy, Sara W Leung, Anita H Corbett, Kenneth H Moberg

{"title":"The RNA-binding protein Nab2 regulates levels of the RhoGEF Trio to govern axon and dendrite morphology.","authors":"Carly L Lancaster, Pranav S Yalamanchili, Jordan N Goldy, Sara W Leung, Anita H Corbett, Kenneth H Moberg","doi":"10.1091/mbc.E24-04-0150","DOIUrl":"10.1091/mbc.E24-04-0150","url":null,"abstract":"The Drosophila RNA-binding protein (RBP) Nab2 acts in neurons to regulate neurodevelopment and is orthologous to the human intellectual disability-linked RBP, ZC3H14. Nab2 governs axon projection in mushroom body neurons and limits dendritic arborization of class IV sensory neurons in part by regulating splicing events in ∼150 mRNAs. Analysis of the Sex-lethal (Sxl) mRNA revealed that Nab2 promotes an exon-skipping event and regulates m6A methylation on Sxl pre-mRNA by the Mettl3 methyltransferase. Mettl3 heterozygosity broadly rescues Nab2null phenotypes implying that Nab2 acts through similar mechanisms on other RNAs, including unidentified targets involved in neurodevelopment. Here, we show that Nab2 and Mettl3 regulate the removal of a 5'UTR (untranslated region) intron in the trio pre-mRNA. Trio utilizes two GEF domains to balance Rac and RhoGTPase activity. Intriguingly, an isoform of Trio containing only the RhoGEF domain, GEF2, is depleted in Nab2null nervous tissue. Expression of Trio-GEF2 rescues projection defects in Nab2null axons and dendrites, while the GEF1 Rac1-regulatory domain exacerbates these defects, suggesting Nab2-mediated regulation Trio-GEF activities. Collectively, these data indicate that Nab2-regulated processing of trio is critical for balancing Trio-GEF1 and -GEF2 activity and show that Nab2, Mettl3, and Trio function in a common pathway that shapes axon and dendrite morphology.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580246","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

ASCB statement of commitment to diversity, equity, and inclusion. ASCB 关于多样性、公平和包容性承诺的声明。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 DOI: 10.1091/mbc.E24-06-0244

Sandra A Murray, Erika L F Holzbaur, Mary Munson, Daniela Cimini, Timothy F Lane, Rebecca Alvania, Derek A Applewhite, Fred Chang, Elizabeth H Chen, William C Earnshaw, Chantell S Evans, Rong Li, Beata E Mierzwa, Tiffany Oliver, Verónica A Segarra, Ahna R Skop, Lesley N Weaver, David J Asai, Michael Boyce, Maria Elena Zavala, Latanya Hammonds-Odie, Jim Vigoreaux

引用次数: 0

HSPA8 inhibitors augment cancer chemotherapeutic effectiveness via potentiating necroptosis. HSPA8 抑制剂可通过加强坏死作用提高癌症化疗效果。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 Epub Date: 2024-07-03 DOI: 10.1091/mbc.E24-04-0194

Erpeng Wu, Chenlu Wu, Kelong Jia, Shen'ao Zhou, Liming Sun

{"title":"HSPA8 inhibitors augment cancer chemotherapeutic effectiveness via potentiating necroptosis.","authors":"Erpeng Wu, Chenlu Wu, Kelong Jia, Shen'ao Zhou, Liming Sun","doi":"10.1091/mbc.E24-04-0194","DOIUrl":"10.1091/mbc.E24-04-0194","url":null,"abstract":"Our recent work has uncovered a novel function of HSPA8 as an amyloidase, capable of dismantling the RHIM-containing protein fibrils to suppress necroptosis. However, the impact of HSPA8 inhibitors on cancer regression via necroptosis remains unexplored. In this study, we conducted a comprehensive investigation to assess the potential of HSPA8 inhibitors in enhancing necroptosis both in vitro and in vivo. Our findings indicate that pharmacologic inhibition of HSPA8, achieved either through VER (VER-155008) targeting the nucleotide binding domain or pifithrin-μ targeting the substrate binding domain of HSPA8, significantly potentiates necroptosis induced by diverse treatments in cellular assays. These inhibitors effectively disrupt the binding of HSPA8 to the RHIM protein, impeding its regulatory function on RHIM amyloid formation. Importantly, HSPA8 inhibitors significantly enhanced cancer cell sensitivity to microtubule-targeting agents (MTAs) in vitro, while reversing chemoresistance and facilitating tumor regression by augmenting necroptosis in vivo. Our findings suggest a promising therapeutic approach to cancer through necroptosis modulation via HSPA8 targeting, particularly in combination with MTA drugs for enhanced treatment efficacy.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498444","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 novel protein Moat prevents ectopic epithelial folding by limiting Bazooka/Par3-dependent adherens junctions. 一种新型蛋白质 Moat 可通过限制 Bazooka/Par3 依赖性粘连接头来防止上皮异位折叠。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 Epub Date: 2024-06-26 DOI: 10.1091/mbc.E24-04-0177

Lingkun Gu, Rolin Sauceda, Jasneet Brar, Ferdos Fessahaye, Minsang Joo, Joan Lee, Jacqueline Nguyen, Marissa Teng, Mo Weng

{"title":"A novel protein Moat prevents ectopic epithelial folding by limiting Bazooka/Par3-dependent adherens junctions.","authors":"Lingkun Gu, Rolin Sauceda, Jasneet Brar, Ferdos Fessahaye, Minsang Joo, Joan Lee, Jacqueline Nguyen, Marissa Teng, Mo Weng","doi":"10.1091/mbc.E24-04-0177","DOIUrl":"10.1091/mbc.E24-04-0177","url":null,"abstract":"Contractile myosin and cell adhesion work together to induce tissue shape changes, but how they are patterned to achieve diverse morphogenetic outcomes remains unclear. Epithelial folding occurs via apical constriction, mediated by apical contractile myosin engaged with adherens junctions, as in Drosophila ventral furrow formation. While it has been shown that a multicellular gradient of myosin contractility determines folding shape, the impact of multicellular patterning of adherens junction levels on tissue folding is unknown. We identified a novel Drosophila gene moat essential for differential apical constriction and folding behaviors across the ventral epithelium which contains both folding ventral furrow and nonfolding ectodermal anterior midgut (ectoAMG). We show that Moat functions to downregulate polarity-dependent adherens junctions through inhibiting cortical clustering of Bazooka/Par3 proteins. Such downregulation of polarity-dependent junctions is critical for establishing a myosin-dependent pattern of adherens junctions, which in turn mediates differential apical constriction in the ventral epithelium. In moat mutants, abnormally high levels of polarity-dependent junctions promote ectopic apical constriction in cells with low-level contractile myosin, resulting in expansion of infolding from ventral furrow to ectoAMG, and flattening of ventral furrow constriction gradient. Our results demonstrate that tissue-scale distribution of adhesion levels patterns apical constriction and establishes morphogenetic boundaries.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458064","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

Verteporfin inhibits TGF-β signaling by disrupting the Smad2/3-Smad4 interaction. Verteporfin 通过破坏 Smad2/3-Smad4 的相互作用来抑制 TGF-β 信号传导。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-07-01 Epub Date: 2024-05-02 DOI: 10.1091/mbc.E24-02-0073

Junxiu Nong, Shengqiang Shen, Fan Hong, Fan Xiao, Lingtian Meng, Pilong Li, Xiaoguang Lei, Ye-Guang Chen

{"title":"Verteporfin inhibits TGF-β signaling by disrupting the Smad2/3-Smad4 interaction.","authors":"Junxiu Nong, Shengqiang Shen, Fan Hong, Fan Xiao, Lingtian Meng, Pilong Li, Xiaoguang Lei, Ye-Guang Chen","doi":"10.1091/mbc.E24-02-0073","DOIUrl":"10.1091/mbc.E24-02-0073","url":null,"abstract":"Transforming growth factor-β (TGF-β) signaling plays a crucial role in pathogenesis, such as accelerating tissue fibrosis and promoting tumor development at the later stages of tumorigenesis by promoting epithelial-mesenchymal transition (EMT), cancer cell migration, and invasion. Targeting TGF-β signaling is a promising therapeutic approach, but nonspecific inhibition may result in adverse effects. In this study, we focus on the Smad2/3-Smad4 complex, a key component in TGF-β signaling transduction, as a potential target for cancer therapy. Through a phase-separated condensate-aided biomolecular interaction system, we identified verteporfin (VP) as a small-molecule inhibitor that specifically targets the Smad2/3-Smad4 interaction. VP effectively disrupted the interaction between Smad2/3 and Smad4 and thereby inhibited canonical TGF-β signaling, but not the interaction between Smad1 and Smad4 in bone morphogenetic protein (BMP) signaling. Furthermore, VP exhibited inhibitory effects on TGF-β-induced EMT and cell migration. Our findings indicate a novel approach to develop protein-protein interaction inhibitors of the canonical TGF-β signaling pathway for treatments of related diseases.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11244160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861932","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