Wnt信号通路在神经系统发育和神经系统疾病过程中的作用

Wnt信号通路是广泛存在于多细胞真核生物中一条高度保守的信号通路,参与调控多种生命过程而且能够起到决定性的导向作用。脑外伤、脑卒中以及神经退行性疾病如阿尔茨海默病（AD）、帕金森病（PD）等仍是全世界面临的危害人类健康的重大疾病,呈现高致死率和高致残率。近几年,Wnt信号通路因其在神经发育和中枢神经系统（CNS）疾病中的重要作用而逐渐受到重视。全面而深入地阐明Wnt信号通路作用的分子机制可能为CNS疾病的预防和治疗提供新的思路和方法。本文概述了经典Wnt／β-catenin信号通路对神经细胞发育和死亡的调控作用及其与中枢神经系统疾病的关系。     

依赖于Smad的TGFβ信号通路与结直肠癌关系的研究进展

依赖于Smad的转化生长因子(TGF)β信号通路中各重要组成部分的异常与肿瘤血管生成、上皮间质转化、免疫逃逸相关,而这些因素促进了结直肠癌的发生、发展.阻断依赖于Smad的TGFβ信号通路可用于结直肠癌的临床治疗.本文综述依赖于Smad的TGFβ信号通路以及其与结直肠癌之间的联系.     

Wnt信号通路在B细胞相关血液系统肿瘤中的研究现状

Wnt信号通路是一种高度保守的信号通路,在包括免疫细胞在内的多种细胞的发育、活化、再生和下调中发挥重要作用。生理条件下,骨髓造血干细胞(HSC)通过自我更新,并不断分化为新的成熟免疫细胞,继而维持和调节免疫系统平衡。Wnt信号通路在B细胞发育活化中通过直接或间接的方式发挥作用,而该信号通路的异常与血液系统肿瘤的发生发展密切相关。目前靶向Wnt信号通路中信号分子治疗血液系统肿瘤的药物已进入临床试验阶段,可能为治疗复发难治性血液系统肿瘤提供新的选择。本文对Wnt信号通路在B淋巴细胞发育活化及其在B细胞相关血液系统肿瘤中作用的研究现状进行了综述,以期为相关血液系统肿瘤的临床治疗提供借鉴。     

Notch信号通路在结直肠肿瘤干细胞中的作用

结直肠癌是消化系统中最常见的恶性肿瘤之一,有研究报道Notch信号通路在结直肠肿瘤干细胞形成结直肠癌中起关键作用,然而其对结直肠肿瘤干细胞的作用机制尚不清楚。如能清楚地了解Notch信号通路在结直肠肿瘤干细胞中的作用,可为以后研发以Notch信号通路联合肿瘤干细胞为治疗靶点的新途径提供参考。本研究就Notch信号通路在结直肠肿瘤干细胞中作用的相关文献加以综述。     

Wnt信号转导通路及其与肿瘤相关的调节因素研究进展

<正>细胞信号转导途径及其形成的信号转导网络是调控细胞生命活动的基础,是维持机体健康或疾病发生、发展的根本因素。Wnt信号通路为一条多环节、多作用位点的开放式途径,通过不同的Wnt配体与靶细胞上不同受体或复合受体特异性结合,以及各通路之间的相互作用等方式,最终形成一个复杂的Wnt蛋白质作用网络,从而决定细胞内不同的信号级联反应。Wnt通路在发育和随环境的自我平衡中发挥特殊而复杂的机能。目前依赖于分子、细胞和组织水平的整体     

Wnt信号通路在肺癌治疗方面的研究进展

肺癌是世界范围内最常见的恶性肿瘤之一,严重威胁着人类生命健康,其发病的分子机制尚未完全明确,目前已证实Wnt通路的异常活化参与肺癌的发生过程。本文就Wnt信号在肺癌发生中的作用,Wnt信号显示其恶性潜能所用到的分子机制,以及在Wnt信号通路中能作为药物研发和肺癌治疗靶点的各种节点作一综述。     

靶向β-catenin/TCF4相互作用抑制剂在肿瘤分子治疗中的研究进展

经典Wnt信号通路的异常活化与恶性肿瘤的发生与发展密切相关,β-catenin/TCF4 (T-cell factor4)相互作用作为Wnt信号通路中的"分子开关",促进了肿瘤的转移与复发,被认为是广谱高选择性抗肿瘤药物开发的理想靶标之一.目前,PKF222-815、iCRT3/5/14、LF3和血根碱等靶向β-cat...     

Wnt/β-catenin信号转导通路在瘢痕疙瘩形成中的作用机制研究

目的 了解Wnt/β-catenin信号转导通路在瘢痕疙瘩原代成纤维细胞中关键蛋白和mRNA水平,探讨其在瘢痕疙瘩形机制中的作用.方法 采用组织块培养法进行原代成纤维细胞培养,通过Western Blot和RT-PCR法分别检测正常皮肤以及瘢痕疙瘩成纤维细胞中Wnt/β-catenin信号转导通路中相关信号分子Wnt5...     

维生素D对骨髓基质干细胞成骨分化的分子调控研究进展

骨髓基质干细胞(MSCs)是骨髓基质的组成成分,在骨骼的发育和代谢平衡中起重要作用。该文总结并综述了维生素D及其活性形式1,25二羟基维生素D_3[1,25(OH)_2D_3]通过Wnt信号通路、Wnt5a/ROR2轴、BMP/TGF-β/Samd信号通路、ROS/ERK信号通路对MSCs成骨分化的分子调控,阐明了维生素D对MSCs代谢调控的分子信号通路。     

基于GEO结直肠癌芯片数据的生物信息学分析

目的 利用生物信息学分析方法,挖掘结直肠癌(CRC)的关键基因并探索其发病机制.方法 在公共基因芯片数据库(GEO)中下载结直肠癌表达谱芯片数据,在GCBI实验室中筛选出结直肠癌显著差异的基因,分别对显著差异基因作GO富集分析、KEGG通路分析、蛋白质相互作用(PPI)网络分析.进一步利用cytoscape将PPI结果建立互作模块.结果 通过差异分析得出在正常结直肠组织、结直肠腺瘤、结直肠癌中表达量逐步明显下调的基因有492个,逐步明显上调的有248个,共有740个显著差异基因.GO富集分析主要体现在各种代谢过程、细胞增殖、信号调节、RNA聚合酶Ⅱ转录因子活性等.KEGG信号通路主要富集在癌症转录失调、细胞周期及p53信号通路等.并利用互作模型筛选出CDK1、MCM2、CDC6、CCNA1、CCNB2、CDKN1B、ORC1、E2F1、CHEK1、PCNA等45个与结直肠癌发生发展关系密切的关键基因.关键基因主要富集在细胞周期、病毒致癌机理、癌症相关、p53及PI3K-Akt等信号通路.结论 通过生物信息学对基因芯片数据的分析,能获取结直肠癌的关键基因及其相关通路,为后续研究提供依据.     

Wnt signaling in renal cancer

About one fourth of people diagnosed with kidney cancer in 2007, are expected to die of this disease within 5 years from the date of diagnosis. Recent years have produced novel drugs, some with FDA approval, and many in clinical trials, all showing very discrete results. Failure in finding effective treatments to improve survival with drugs mainly targeting VEGF and its downstream effectors, urges to shift the drug development targets to other unexploited pathways shown to be also involved in renal cancer. Several studies show alterations in the Wnt signaling pathway, many of which differ from those implicated in other human cancers. Unlike colorectal or hepatocellular carcinomas, where APC and axin mutations, respectively, are the main Wnt signaling deregulating event, renal carcinomas seem to be affected by other factors. Recent studies have presented VHL, a tumor suppressor gene strongly associated with renal cell carcinoma, as a beta-catenin target. This confirms that Wnt signaling is likely playing a central role during renal carcinoma development, which needs to be considered and addressed to treat this disease. This review outlines briefly the molecular biology of the most common renal cancers and the drug treatments currently used to treat the disease. The canonical Wnt pathway is reviewed more carefully adding specific features in a renal carcinoma context, which present potential targets for drug development and biomarker use.     

Targeting the most upstream site of Wnt signaling pathway provides a strategic advantage for therapy in colorectal cancer

The Wnt signaling pathway has important functions in development, tissue homeostasis, and regeneration. Deregulation of canonical Wnt/beta-catenin signaling is frequently found in various human cancers, particularly in colorectal cancer, and non-canonical Wnt signaling pathways also have been implicated in neoplasia. Colorectal cancer is a multi-pathway disease. Activation of Wnt signaling by both genetic and epigenetic alterations has been found to be important for both, initiation and progression of colorectal cancer. In addition, since Wnt signaling results in diverse downstream intracellular events, targeted inhibition of Wnt/beta-catenin signaling at the most upstream site of this pathway is a rational and an advantageous new approach for the therapy of colorectal cancer.     

Targeting the Wnt signaling pathway in colorectal cancer

Introduction: The treatment of patients with advanced colorectal cancer still remains challenging, and identification of new target molecules and therapeutic avenues remains a priority. The great majority of colorectal cancers have mutations in one of two genes involved in the Wnt signaling pathway: the adenomatous polyposis coli (APC) and β-catenin (CTNNB1) genes. Up to now, however, no therapeutics for targeting this pathway have been established.

Areas covered: This review article begins with a brief summary of Wnt signaling from the viewpoints of genetics, cancer stem cell biology, and drug development. We then overview current attempts to develop drugs directed at various components of the Wnt signaling pathway.

Expert opinion: APC is a tumor suppressor, and therefore only downstream signal transducers of the APC protein can be considered as targets for pharmaceutical intervention. TRAF2 and NCK-interacting protein kinase (TNIK) was identified as the most downstream regulator of Wnt signaling by two independent research groups, and several classes of small-molecule inhibitors targeting this protein kinase have been developed. TNIK is a multifunctional protein with actions that extend beyond Wnt signaling regulation. Such TNIK inhibitors are expected to have a large variety of clinical applications.     

Wnt/beta-catenin signaling pathway as a novel cancer drug target

Wnt proteins are a large family of secreted glycoproteins. Wnt proteins bind to the Frizzled receptors and LRP5/6 co-receptors, and through stabilizing the critical mediator beta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. Deregulation of the canonical Wnt/beta-catenin signaling pathway, mostly by inactivating mutations of the APC tumor suppressor, or oncogenic mutations of beta-catenin, has been implicated in colorectal tumorigenesis. Although oncogenic mutations of beta-catenin have only been discovered in a small fraction of non-colon cancers, elevated levels of beta-catenin protein, a hallmark of activated canonical Wnt pathway, have been observed in most common forms of human malignancies, indicating that activation of this pathway may play an important role in tumor development. Over the past 15 years, our understanding of this signaling pathway has significantly improved with the identification of key regulatory proteins and the important downstream targets of beta-catenin/Tcf transactivation complex. Given the fact that Wnt/beta-catenin signaling is tightly regulated at multiple cellular levels, the pathway itself offers ample targeting nodal points for cancer drug development. In this review, we discuss some of the strategies that are being used or can be explored to target key components of the Wnt/beta-catenin signaling pathway in rational cancer drug discovery.     

Wnt信号通路诱导肿瘤细胞上皮间质转化的研究进展

肿瘤细胞发生上皮间质转化(epithelial-mesenchymaltransition,EMT)从而具有侵袭转移的能力,是肿瘤发展的一个重要过程。既往研究发现Wnt信号通路调节控制着许多生命过程,也发现其是诱导EMT不可缺少的重要通路。通过对Wnt信号分子的调控,可以有效的阻断甚至逆转EMT。Wnt诱导EMT发生发展过程的研究,也为抗肿瘤新药开发提供了新思路,推动了药物的研发。该文旨在对近年Wnt信号通路诱导EMT的研究做一综述。     

结肠癌患者Wnt信号通路的变化和作用

目的探讨结肠癌患者Wnt信号通路的变化情况及其作用意义。方法利用Human Ge-nome U133Plus2.0基因芯片对结肠正常黏膜组织和癌组织基因表达谱进行检测,分析Wnt信号通路基因表达变化情况。结果Wnt信号通路中FRP、Frizzled、CK2、p53、PP2A、CKIα、JNK、CaMKII、CaN、c-jun、cyc-D等关键基因均呈下调,调控着细胞周期、基因转录等。结论Wnt信号通路可能是调控结肠癌演变过程的重要信号通路之一。     

New perspectives on β-catenin control of cell fate and proliferation in colon cancer

Colorectal cancer is a major health problem worldwide. Aberrant activation of the Wingless-type mouse mammary tumor virus integration site family(Wnt)/β-catenin signaling pathway is the most common and initial alteration in sporadic colorectal tumors. Numerous experimental studies have indicated that β-catenin is a key regulator of colorectal cancer. Indeed, β-catenin activity was shown to designate colon cancer stem cells (CSC) and is, therefore, an attractive target for new therapeutic agents. Thus, it is necessary to further understand its biology and search for effective therapy. Here we review the current literature regarding the functions of β-catenin control of intestinal cell fate and proliferation. Further, we provide a brief commentary on our current understanding of the role that β-catenin plays in colorectal tumor. These results show that β-catenin may serve as a good diagnosis biomarker of early-stage tumor development and a novel potential therapeutic target for colon cancer.     

乳腺癌中Wnt信号通路及WIF1基因的研究进展

Wnt信号通路在乳腺癌的发生发展中起重要作用,参与成体细胞的增殖分化和凋亡。β-catenin的异常表达是乳腺癌发生发展过程中的重要因子,这个过程可能是通过激活cyclin D1实现的。E-钙粘蛋白是关系乳腺癌发展与预后的关键因子,WIF1是Wnt通路中的抑癌基因,对肿瘤的发生发展起着重要作用。本文从Wnt通路组成、Wnt通路的抑制剂和调控及其与乳腺癌的关系作一综述。