更新于：2024-05-01

SOX18

SRY-box transcription factor 18

更新于：2024-05-01

基本信息

别名

SOX18、SRY-box transcription factor 18、Transcription factor SOX-18

简介

Transcriptional activator that binds to the consensus sequence 5'-AACAAAG-3' in the promoter of target genes and plays an essential role in embryonic cardiovascular development and lymphangiogenesis. Activates transcription of PROX1 and other genes coding for lymphatic endothelial markers. Plays an essential role in triggering the differentiation of lymph vessels, but is not required for the maintenance of differentiated lymphatic endothelial cells. Plays an important role in postnatal angiogenesis, where it is functionally redundant with SOX17. Interaction with MEF2C enhances transcriptional activation. Besides, required for normal hair development.

关联

100 项与 SOX18 相关的临床结果

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100 项与 SOX18 相关的转化医学

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0 项与 SOX18 相关的专利（医药）

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243

项与 SOX18 相关的文献（医药）

2024-02-17·General and comparative endocrinology

Mechanistic study of transcription factor Sox18 during heart development.

Article

作者: Jianxin Liang ; Imtiaz Ul Hassan ; Man Yee Cheung ; Lei Feng ; Yi-Jyun Lin ; Qi Long ; Chengdong Wang ; Yuyue Ding ; Ziqing Wang ; Yuan Zhang ; Yulong Li ; Donghao Guo ; Xiaofang Guo ; Thomas Chi Bun Wong ; Muhammad Kaleem Samma ; Zixin Rong ; Xufeng Qi ; Dongqing Cai ; Sai-Ming Ngai ; Hui Zhao

Heart development is a delicate and complex process regulated by coordination of various signaling pathways. In this study, we investigated the role of sox18 in heart development by modulating Wnt/β-Catenin signaling pathways. Our spatiotemporal expression analysis revealed that sox18 is mainly expressed in the heart, branchial arch, pharyngeal arch, spinal cord, and intersegmental vessels at the tailbud stage of Xenopus tropicalis embryo. Overexpression of sox18 in the X. tropicalis embryos causes heart edema, while loss-of-function of sox18 can change the signal of developmental heart marker gata4 at different stages, suggesting that sox18 plays an essential role in the development of the heart. Knockdown of SOX18 in human umbilical vein endothelial cells suggests a link between Sox18 and β-CATENIN, a key regulator of the Wnt signaling pathway. Sox18 negatively regulates islet1 and tbx3, the downstream factors of Wnt/β-Catenin signaling, during the linear heart tube formation and the heart looping stage. Taken together, our findings highlight the crucial role of Sox18 in the development of the heart via inhibiting Wnt/β-Catenin signaling.

2023-11-27·The EMBO journal

GPNMB⁺ Gal-3⁺ hepatic parenchymal cells promote immunosuppression and hepatocellular carcinogenesis.

Article

作者: Yan Meng ; Qiudong Zhao ; Yan Sang ; Jianping Liao ; Fei Ye ; Shuping Qu ; Pingping Nie ; Liwei An ; Weihong Zhang ; Shi Jiao ; Aimin Huang ; Zhaocai Zhou ; Lixin Wei

Hepatocellular carcinoma (HCC) formation is a multi-step pathological process that involves evolution of a heterogeneous immunosuppressive tumor microenvironment. However, the specific cell populations involved and their origins and contribution to HCC development remain largely unknown. Here, comprehensive single-cell transcriptome sequencing was applied to profile rat models of toxin-induced liver tumorigenesis and HCC patients. Specifically, we identified three populations of hepatic parenchymal cells emerging during HCC progression, termed metabolic hepatocytes (HC^Meta ), Epcam⁺ population with differentiation potential (EP^+Diff ) and immunosuppressive malignant transformation subset (MT^Immu ). These distinct subpopulations form an oncogenic trajectory depicting a dynamic landscape of hepatocarcinogenesis, with signature genes reflecting the transition from EP^+Diff to MT^Immu . Importantly, GPNMB⁺ Gal-3⁺ MT^Immu cells exhibit both malignant and immunosuppressive properties. Moreover, SOX18 is required for the generation and malignant transformation of GPNMB⁺ Gal-3⁺ MT^Immu cells. Enrichment of the GPNMB⁺ Gal-3⁺ MT^Immu subset was found to be associated with poor prognosis and a higher rate of recurrence in patients. Collectively, we unraveled the single-cell HCC progression atlas and uncovered GPNMB⁺ Gal-3⁺ parenchymal cells as a major subset contributing to the immunosuppressive microenvironment thus malignance in HCC.

2023-09-19·Cells

Lymphatic Defects in Zebrafish sox18 Mutants Are Exacerbated by Perturbed VEGFC Signaling, While Masked by Elevated sox7 Expression.

Article

作者: Silvia Moleri ; Sara Mercurio ; Alex Pezzotta ; Donatella D'Angelo ; Alessia Brix ; Alice Plebani ; Giulia Lini ; Marialaura Di Fuorti ; Monica Beltrame

Mutations in the transcription factor-coding gene SOX18, the growth factor-coding gene VEGFC and its receptor-coding gene VEGFR3/FLT4 cause primary lymphedema in humans. In mammals, SOX18, together with COUP-TFII/NR2F2, activates the expression of Prox1, a master regulator in lymphatic identity and development. Knockdown studies have also suggested an involvement of Sox18, Coup-tfII/Nr2f2, and Prox1 in zebrafish lymphatic development. Mutants in the corresponding genes initially failed to recapitulate the lymphatic defects observed in morphants. In this paper, we describe a novel zebrafish sox18 mutant allele, sa12315, which behaves as a null. The formation of the lymphatic thoracic duct is affected in sox18 homozygous mutants, but defects are milder in both zygotic and maternal-zygotic sox18 mutants than in sox18 morphants. Remarkably, in sox18 mutants, the expression of the closely related sox7 gene is elevated where lymphatic precursors arise. Sox7 could thus mask the absence of a functional Sox18 protein and account for the mild lymphatic phenotype in sox18 mutants, as shown in mice. Partial knockdown of vegfc exacerbates lymphatic defects in sox18 mutants, making them visible in heterozygotes. Our data thus reinforce the genetic interaction between Sox18 and Vegfc in lymphatic development, previously suggested by knockdown studies, and highlight the ability of Sox7 to compensate for Sox18 lymphatic dysfunction.

项与 SOX18 相关的新闻（医药）

2024-03-06

·奇点网

把这个SOX18往死里打！

*仅供医学专业人士阅读参考介导免疫抑制、不利抗癌治疗的靶点，按说这些年来奇点糕见识得够多了，但大多数靶点都算比较“单纯”，比如只会调控一类免疫抑制细胞。所以假如出现了影响多种免疫抑制细胞的靶点，该怎么办呢？往死里打啊！近日，华中科技大学同济医学院附属同济医院夏丽敏课题组在Gastroenterology期刊发表的最新研究成果，就揭示了肝细胞癌（HCC）中存在的一个“找打”型靶点——转录因子SOX18，它会同时促进肿瘤相关巨噬细胞（TAMs）和调节性T细胞（Tregs）向HCC微环境中大量浸润，进而介导微环境免疫抑制、促进HCC的进展和远处转移。研究显示，SOX18表达水平会在TGF-β1-Smad2/3轴的诱导下发生上调，进而通过转录激活PD-L1和趋化因子CXCL12，促进TAMs和Tregs在HCC微环境中大量浸润，抑制CD8+T细胞对癌细胞的毒性杀伤；针对上述调节机制中的关键环节，如使用CXCR4（CXCL12配体）抑制剂或TGFβR1抑制剂，即可破解SOX18介导的免疫抑制，增敏现有免疫治疗[1]。论文核心内容总结其实，SOX18可以说是协助HCC发生发展的“惯犯”，早在2015年就有我国学者发现，SOX18与HCC患者不良预后有关，将其敲除可抑制HCC细胞的迁移和侵袭能力[2]；开展本次研究的夏丽敏课题组则在2019年的一篇论文中揭示，SOX18可参与促进HCC远处转移的正反馈通路，FGF19、FGFR4两种成纤维细胞生长因子（FGF）/受体是它的共犯[3]。但随着HCC治疗全面进入免疫治疗时代，SOX18在影响免疫应答方面的罪行也就此浮出了水面。在此次研究中，研究者们首先分析了过表达SOX18对两种HCC模型小鼠肿瘤内免疫细胞组分的影响，既然之前发现SOX18过表达与HCC不良预后有关，那细胞毒性CD8+T细胞的浸润减少就完全不出所料了，但TAMs和Tregs同时增多可不能等闲视之。基于RNA单细胞测序结果的差异表达基因（DEGs）分析，在过表达SOX18改变HCC微环境内免疫细胞组成的同时，富集表达的基因集中于上皮-间质转化和免疫相关通路；研究者们又用染色质免疫沉淀法（ChIP）作进一步筛选，确认SOX18会在CD274（编码PD-L1）和CXCL12基因的启动子区域显著富集，结合并上调两个基因的表达水平。SOX18可上调CD274和CXCL12的表达水平SOX18上调PD-L1表达的影响显而易见，PD-L1也是SOX18介导免疫抑制不可或缺的一环，因此接下来的重点是分析上调CXCL12表达的影响：实验显示，CXCL12与其同源受体CXCR4结合，是将TAMs和Tregs募集到HCC免疫微环境的必要条件，而缺少TAMs和Tregs中的任何一方，都会减弱过表达SOX18带来的免疫抑制作用。研究者们推测，在上游激活SOX18以介导免疫抑制的很可能是某种炎性细胞因子，毕竟HCC的发病大多与慢性炎症有关，因此研究者们尝试用各种炎性细胞因子处理HCC细胞系，很快就把TGF-β1给揪了出来，证实它与SOX18表达水平存在剂量依赖性关系；在HCC细胞中，TGF-β1主要是通过促进Smad2/3复合体形成和入核，上调SOX18的表达。TGF-β1-Smad2/3轴介导SOX18的表达水平上调及后续免疫抑制最后，研究者们在自发性肝癌模型小鼠中，进一步证实了SOX18过表达对HCC发生发展有明确的促进作用，敲除SOX18可显著减少TAMs和Tregs浸润，延缓HCC进展及转移，而针对CXCR4、TGFβR1等关键节点进行干预，如使用在研小分子抑制剂，也可起到相似的作用，并与PD-L1抑制剂协同增效，有望在未来组成免疫联合治疗方案。参考文献：[1]Chen J, Feng W, Sun M, et al. TGF-β1 Induced SOX18 Elevation Promotes Hepatocellular Carcinoma Progression and Metastasis through Transcriptionally Upregulating PD-L1 and CXCL12[J]. Gastroenterology, 2024.[2]Wang G, Wei Z, Jia H, et al. Knockdown of SOX18 inhibits the proliferation, migration and invasion of hepatocellular carcinoma cells[J]. Oncology Reports, 2015, 34(3): 1121-1128.[3]Chen J, Du F, Dang Y, et al. Fibroblast Growth Factor 19–Mediated Up‐regulation of SYR‐Related High‐Mobility Group Box 18 Promotes Hepatocellular Carcinoma Metastasis by Transactivating Fibroblast Growth Factor Receptor 4 and Fms‐Related Tyrosine Kinase 4[J]. Hepatology, 2020, 71(5): 1712-1731.本文作者丨谭硕

免疫疗法细胞疗法

2022-07-06

·生物谷

Cell子刊：中南大学李吉团队等发现治疗雄性激素性脱发新方法，可激活毛囊再生

目前全世界有数以亿计的男性，女性甚至是儿童饱受脱发困扰，遗传、衰老、分娩、癌症治疗、烧伤以及压力等都可能导致脱发。据悉，研究团队已经提交了关于使用 SCUBE3 及其相关分子刺激毛发生长的专利申请。Maksim Plikus 教授也将在自己的实验室及其创立的生物技术公司 Amplifica Holdings Group 进行后续研究。