Wnt16b基因扩增影响细胞增殖及肿瘤微环境的研究进展

Wnt蛋白家族是一类在进化上高度保守的家族,与胚胎发育、器官分化相关,在细胞的生长、增殖、分化及凋亡等生物学行为方面发挥重要的调控作用.研究显示,Wnt信号通路紊乱与许多疾病尤其是肿瘤密切相关.Wnt16b作为Wnt蛋白家族的一员,在骨骼的生长分化过程中起关键作用.近年研究发现,Wnt16b基因在多种肿瘤组织中高扩增,提示Wnt16b基因可能在肿瘤的发展、迁移、化疗耐药等方面起重要作用.本文重点就Wnt16b基因扩增与细胞增殖及肿瘤微环境的关联研究进行综述.     

基于Wnt/β-catenin信号通路治疗骨关节炎研究热点及应用前景

文题释义：Wnt信号通路：Wnt是Wingless/Integrated的缩写,由配体蛋白质Wnt和膜蛋白受体结合,激发的一组多下游通道的信号转导的途径,该信号通路在不同的动物物种间极为相似,遗传学上具有高度保守性。通过该途径,细胞表面受体胞内段将活化,将细胞外的信号传递到细胞内。表现为两种信号传导方式,分别是胞间交流(旁分泌)和自体细胞交流(自分泌),经典代表有：Wnt/β-catenin信号通路、平面细胞极性通路(Wnt/PCP通路)和Wnt/Ca²⁺通路。 骨硬化蛋白：由Sost基因编码,是一种分泌型半胱氨酸结蛋白,是Wnt共受体和低蛋白脂蛋白相关受体蛋白5 /低蛋白脂蛋白相关受体蛋白6相关受体的拮抗剂,作用于通路的上游,抑制Wnt 信号通路,从而起到软骨保护作用。背景：Wnt/β-catenin信号通路在骨关节炎的发展中起着重要的作用。 目的：基于Wnt/β-catenin信号通路,对骨关节炎的研究进展做一综述。方法：查阅PubMed、中国知网和万方数据库,以“catenin;wnt;osteoarthritis;arthritis;degenerative;arthritides;deformans;pathway;wnt signaling;signaling pathway;wnt signaling pathways;wnt beta catenin signaling pathway;canonical wnt pathway;canonical wnt;骨关节炎”为检索词,分别组合检索,查找Wnt/β-catenin信号通路治疗骨关节炎的文献,最终纳入74篇文献进行分析。结果与结论：基于Wnt/β-catenin信号通路治疗骨关节炎,主要途径有天然的拮抗剂、小分子抑制剂、激动剂、中草药和药物重新定位等方面。药物作用途径通过激活或者抑制Wnt/β-catenin信号通路,对软骨起到保护作用。通过Wnt/β-catenin信号通路治疗骨关节炎,目前处于实验性研究阶段,但具有较好应用前景。如何精准调控通路,更好的转化应用,有望成为未来研究的热点。ORCID: 0000-0002-9553-7171(贝涛) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Wnt信号通路成员APC蛋白和β-Catenin与肿瘤的关系

APC蛋白和β- catenin是 Wnt信号通路β- catenin降解复合体的重要组分 ,在 Wnt信号通路异常导致甲状腺肿瘤的发生中 ,它们发挥重要的作用     

Wnt信号通路成员APC蛋白和β—catenin与肿瘤的关系

APC蛋白和β—catenin是Wnt信号通路β—catenin降解复合体的重要组分，在Wnt信号通路异常导致甲状腺肿瘤的发生中，它们发挥重要的作用。     

Wnt/β-catenin信号转导途径与宫颈癌

信号转导通路异常在肿瘤发生、发展过程中发挥着作用,其中Wnt/β-catenin信号转导通路在调控细胞的生长和分化、胚胎发育及肿瘤的发生发展起重要作用.Wnt/β-catenin信号转导通路异常与宫颈癌的发病机制密切相关.     

表皮修复过程中Wnt信号途径的研究进展

Wnt信号通路是一个复杂的蛋白质作用网络,其功能最常见于胚胎发育和癌症,但也参与成年动物的正常生理过程。随着皮肤组织工程的快速发展,关于皮肤创后愈合过程中的Wnt信号的研究也越来越多。目前已知Wnt信号途径在表皮干细胞、表皮生长因子以及毛囊发育等重要表皮修复的相关因素中发挥重要作用,系统地研究Wnt信号途径在皮肤组织中的表达及作用过程具有重要临床意义。本文就近年来Wnt信号途径在表皮修复过程中的研究进展做以下综述。     

Wnt/β-catenin信号传导通路与早期胚胎心脏发育的关系

Wnt/β-catenin信号传导通路是调控细胞增殖、运动、分化的关键途径,在胚胎发育方面起重要作用。研究者发现Wnt信号通路是早期刺激心脏发生的重要调节因素,与早期胚胎的心脏形态发生有密切联系。本文就目前Wnt信号通路与早期胚胎心脏发育的研究进展进行综述。     

Wnt信号通路与非小细胞肺癌的研究进展

Wnt信号通路在人类恶性肿瘤有着重要的调控作用。在非小细胞肺癌(NSCLC)细胞系,抑制Wnt通路能降低肿瘤扩散。Wnt信号因子影响非小细胞肺癌细胞的生长、分化、疾病的预后及化疗抗药性,可作为晚期非小细胞肺癌靶向治疗的新选择。     

APC与XVnt／β-catenin信号转导途径

APC是Wnt信号转导通路的重要组成分子.APC蛋白可控制β-catenin在细胞内的含量,在Wnt信号转导通路中起负向调节作用.APC基因突变或蛋白异常可使Wnt信号转导通路异常激活,多种原癌基因持续转录而导致肿瘤发生.本文主要探讨APC基因失活的机制和对Wnt信号转导通路的影响.     

丙戊酸钠通过上调Wnt/β-catenin信号通路促进培养神经元的生长(英文)

目的:丙戊酸盐(丙戊酸valproic acid,VPA)在过去数十年应用于临床治疗癫痫和偏头痛。然而,母亲怀孕早期使用VPA将大大增加子代罹患孤独症群谱障碍的易感性。鉴于Wnt/β-catenin信号通路对神经元增殖、分化、突起生长及凋亡的重要作用,本文旨在研究VPA在原代培养神经元中对Wnt/β-catenin信号通路的影响。方法:用VPA处理原代培养神经元,以生理盐水处理为对照,运用Western Blot检测Wnt/β-catenin通路相关信号分子Wnt1,Wnt2,WIF-1,Dickkopf 1及效应分子β-catenin的表达变化,同时运用免疫荧光技术观察神经元形态变化。结果:与对照组比较,VPA处理显著增加Wnt1及Wnt2的表达(P<0.05~0.01),而未增加WIF-1及Dickkopf 1的表达(P>0.05);VPA处理也导致Wnt/β-catenin通路活性上调,表现为神经元内β-catenin含量显著上升。此外,与对照组比较,VPA处理促进神经元生长,表现为神经元突起数目(P<0.05~0.01)及总长度显著增加(P<0.05~0.01);Wnt/β-catenin通路抑制剂能部分抑制VPA引起的Wnt/β-catenin通路活性上调及神经元生长。结论:VPA通过上调Wnt/β-catenin信号通路促进神经元生长,可能是VPA增加子代罹患孤独症群谱障碍易感性的原因。     

Wnt信号转导途径与髓母细胞瘤

髓母细胞瘤是多发于儿童小脑的恶性肿瘤,其预后很差。Wnt信号转导途径对多种生物发育、细胞的增殖和分化起着重要的作用,如异常表达或激活该途径会导致各种疾病甚至肿瘤发生。在经典Wnt途径中β-连环蛋白是其关键成员。Wnt蛋白与跨膜受体Fz蛋白结合后，破坏多蛋白降解复合物，积累的β-连环蛋白进入胞核与转录因子Tcf/Lef形成复合体，从而激活下游靶基因。目前研究表明Wnt信号转导途径与髓母细胞瘤的致癌作用密切相关。     

Tankyrase is necessary for canonical Wnt signaling during kidney development

Recent studies using small molecule antagonists have revealed that the poly(ADP‐ribose) polymerases (PARPs) Tankyrase 1 and 2 are critical regulators of canonical Wnt signaling in some cellular contexts. However, the absence of any activity during zebrafish embryogenesis suggested that the tankyrases may not be general/core components of the Wnt pathway. Here, we show that Tnks1 and 2 are broadly expressed during mouse development and are essential during kidney and lung development. In the kidney, blockage of tankyrase activity phenocopies the effect of blocking production of all Wnt ligands. Tankyrase inhibition can be rescued by activation of β‐catenin demonstrating its specificity for the Wnt pathway. In addition, treatment with tankyrase inhibitors appears to be completely reversible in some cell types. These studies suggest that the tankyrases are core components of the canonical Wnt pathway and their inhibitors should enjoy broad usage as antagonists of Wnt signaling. Developmental Dynamics 239:2014–2023, 2010 © 2010 Wiley‐Liss, Inc.     

Wnt signaling: physiology and pathology

Signaling by the Wnt family of secreted glycoproteins has been demonstrated to be essential both in normal embryonic development and in the pathogenesis of a variety of diseases, including cancer. This signaling pathway is exquisitely regulated by a large and complex array of proteins, which act as agonists or antagonists of signal transduction, modulating the Wnt signal extracellularly, in the cytoplasm and in the nucleus. Here, we will briefly review the canonical Wnt signaling pathway and consider molecular defects in Wnt signaling components known to promote uncontrolled cell growth following induction of Wnt signaling. We will also focus on two recently identified factors in this pathway, that seem to act as Wnt signaling antagonists, one functioning in the cytoplasm called Disabled-2 and the other in the nucleus named Chibby.     

Wnt抑制因子-1与Wnt通路和肿瘤发生

Wnt抑制因子-1(WntInhibitoryFactor-1,WIF-1)是近年发现的一种Wnt信号抑制分子。WIF-1的结构已基本清楚,其在生物体内的分布因种属和不同发育时期而异。目前认为,WIF-1可能是Wnt的负反馈调节因子,它可与WNT蛋白直接结合并阻断Wnt信号的传递,而Wnt信号也可通过反馈机制对WIF-1的表达和分布进行调节。研究证实,Wnt通路紊乱可引起肿瘤,在多种存在Wnt通路紊乱的肿瘤中均存在WIF-1表达下调或缺失,WIF-1表达下调的原因是由于wif-1基因启动子区发生高甲基化,采用去甲基化等方法恢复WIF-1的正常表达后可抑制相关肿瘤细胞的生长,甚至导致凋亡。     

Wnt signaling pathway in aging-related tissue fibrosis and therapies

Fibrosis is the final hallmark of pathological remodeling, which is a major contributor to the pathogenesis of various chronic diseases and aging-related organ failure to fully control chronic wound-healing and restoring tissue function. The process of fibrosis is involved in the pathogenesis of the kidney, lung, liver, heart and other tissue disorders. Wnt is a highly conserved signaling in the aberrant wound repair and fibrogenesis, and sustained Wnt activation is correlated with the pathogenesis of fibrosis. In particular, mounting evidence has revealed that Wnt signaling played important roles in cell fate determination, proliferation and cell polarity establishment. The expression and distribution of Wnt signaling in different tissues vary with age, and these changes have key effects on maintaining tissue homeostasis. In this review, we first describe the major constituents of the Wnt signaling and their regulation functions. Subsequently, we summarize the dysregulation of Wnt signaling in aging-related fibrotic tissues such as kidney, liver, lung and cardiac fibrosis, followed by a detailed discussion of its involvement in organ fibrosis. In addition, the crosstalk between Wnt signaling and other pathways has the potential to profoundly add to the complexity of organ fibrosis. Increasing studies have demonstrated that a number of Wnt inhibitors had the potential role against tissue fibrosis, specifically in kidney fibrosis and the implications of Wnt signaling in aging-related diseases. Therefore, targeting Wnt signaling might be a novel and promising therapeutic strategy against aging-related tissue fibrosis.