Hedgehog信号转导通路与肺癌

Hedgehog(Hh)信号通路在胚胎发育期起关键作用,调节细胞的增殖、分化,协调组织器官如皮肤、脑、神经管、肠、附肢及肺等发育过程中的关键步骤.在成年期,Hh通路调控干细胞的增殖,此时Hh通路受到严格的时空限制.近年来研究表明Hh信号通路异常激活与包括肺癌在内的多种肿瘤的发生、发展密切相关,因此可能会成为肿瘤治疗的一个新靶点.现对Hh信号通路的特性及其在肺癌中的研究现状作一综述.     

Hedgehog信号转导通路与肺癌

 【摘要】　Hedgehog（Hh）信号通路在胚胎发育期起关键作用,调节细胞的增殖、分化,协调组织器官如皮肤、脑、神经管、肠、附肢及肺等发育过程中的关键步骤。在成年期,Hh通路调控干细胞的增殖,此时Hh通路受到严格的时空限制。近年来研究表明Hh信号通路异常激活与包括肺癌在内的多种肿瘤的发生、发展密切相关,因此可能会成为肿瘤治疗的一个新靶点。现对Hh信号通路的特性及其在肺癌中的研究现状作一综述。     

Hedgehog信号通路与肿瘤的关系研究进展

Hedgehog（Hh）信号通路在胚胎时期的细胞分化、组织发育及器官形成中扮演重要角色。近年来,Hh信号通路与肿瘤的关系日益受到人们的重视。多项研究结果显示Hh信号通路在多种肿瘤组织与细胞系中异常激活,并与肿瘤的增殖分化、细胞凋亡、血管新生、侵袭转移等密切相关。阻断肿瘤细胞中Hh信号传导通路将为人类肿瘤的治疗提供一个新的有效手段。     

Hedgehog信号通路与肿瘤的关系研究进展

Hedgehog(Hh)信号通路在胚胎时期的细胞分化、组织发育及器官形成中扮演重要角色。近年来,Hh信号通路与肿瘤的关系日益受到人们的重视。多项研究结果显示Hh信号通路在多种肿瘤组织与细胞系中异常激活,并与肿瘤的增殖分化、细胞凋亡、血管新生、侵袭转移等密切相关。阻断肿瘤细胞中Hh信号传导通路将为人类肿瘤的治疗提供一个新的有效手段。     

Hedgehog信号通路与肿瘤

Hedgehog（Hh）信号通路可以调控细胞的增殖、迁移和分化等许多过程,并且在胚胎发育时期起重要作用。根据Hh信号通路激活后是否依赖Gli蛋白发挥生物学效应,可分为经典的Hh/Gli信号通路和非经典的Hh信号通路。其中,非经典的Hh信号通路可通过小G蛋白Rho家族信号和钙离子依赖的信号通路调控细胞骨架形态、细胞增殖、凋亡及迁移;经典与非经典的Hh信号通路形成相互联系的信号通路网络介导Hh信号的功能。Hh信号通路的异常持续的激活是许多肿瘤发生、发展的原因之一,Hh信号通路还与肿瘤干细胞的调控、肿瘤血管形成和肿瘤的侵袭转移密切相关,对Hh信号通路的深入研究有利于以Hh信号通路蛋白为靶点的抗肿瘤药物的研发与应用。     

胃癌Hedgehog通路研究进展

Hedgehog（Hh）信号通路在胚胎组织的分化过程中发挥着重要作用,最近研究认为该信号通路的持续异常激活与肿瘤的发生发展有着密切的关系。已有研究报道胃癌中也存在Hh信号通路的异常活化,并与胃癌的发生、增殖和侵袭转移等过程密切相关。本文就Hh信号通路在胃癌中的研究进展作一系统综述,为完善胃癌的发病机制、诊断及治疗提供新的思路。      

Hedgehog信号通路与胰腺癌

Hedgehog（Hh）信号通路为胰腺胚胎发育所必需,其异常激活是胰腺癌发生发展过程中的重要分子事件。体内外实验显示阻断Hh信号通路可抑制胰腺癌细胞的增殖、浸润、迁移,降低肿瘤转移。最近研究发现阻断Hh信号通路可以清除胰腺癌间质,提高药物输送,联合吉西他滨还可以清除肿瘤干细胞,改善预后。Hh信号通路抑制剂可能给胰腺癌带来新的治疗选择。     

Sonic hedgehog信号通路及其在肺癌中的研究进展

Hedgehog(Hh)信号通路是一种在动物胚胎时期起重要作用的信号通路,目前已经发现该通路的异常激活在多种肿瘤发生中有重要作用.Hh信号通路在肺癌中的配体依赖性激活也在多种肺癌类型中被发现,现简要介绍对该通路及其在肺癌发生中作用的研究进展.     

Hedgehog信号通路与肿瘤的研究新进展

Hedgehog（Hh）信号通路在果蝇中被首次发现。该信号通路能有效调控哺乳动物的胚胎发育过程,此外,在调控细胞的分化、增殖、血管形成及肿瘤形成方面起重要作用。Hh信号通路是一个Hh-Ptch-Smo-Gli的级联反应过程。该通路的配体包括:Hedgehog配体［Sonic Hh（SHh）、Indian Hh（IHh）和Desert Hh（DHh）］,Ptch受体（Ptch1、Ptch2）,Smoothened受体（Smo）,融合同源物（Sufu）的抑制因子,驱动蛋白Kif7,蛋白激酶A（PKA）和环腺苷一磷酸（cAMP）。该级联反应中的终末转录因子Gli调控的下游基因过度表达可能是导致肿瘤产生的关键因素。许多研究者已经发现,Hegehog信号通路与一系列人类实体瘤的形成关系密切。本文就近年来Hedgehog信号通路及其与肿瘤关系的研究进行综述。     

Sonic hedgehog信号通路及其在肺癌中的研究进展

Hedgehog(Hh)信号通路是一种在动物胚胎时期起重要作用的信号通路，目前已经发现该通路的异常激活在多种肿瘤发生中有重要作用。Hh信号通路在肺癌中的配体依赖性激活也在多种肺癌类型中被发现，现简要介绍对该通路及其在肺癌发生中作用的研究进展。     

Clinical implications of hedgehog signaling pathway inhibitors

Hedgehog was first described in Drosophila melanogaster by the Nobel laureates Eric Wieschaus and Christiane Nüsslein-Volhard. The hedgehog (Hh) pathway is a major regulator of cell differentiation, proliferation, tissue polarity, stem cell maintenance, and carcinogenesis. The first link of Hh signaling to cancer was established through studies of a rare familial disease, Gorlin syndrome, in 1996. Follow-up studies revealed activation of this pathway in basal cell carcinoma, medulloblastoma and, leukemia as well as in gastrointestinal, lung, ovarian, breast, and prostate cancer. Targeted inhibition of Hh signaling is now believed to be effective in the treatment and prevention of human cancer. The discovery and synthesis of specific inhibitors for this pathway are even more exciting. In this review, we summarize major advances in the understanding of Hh signaling pathway activation in human cancer, mouse models for studying Hh-mediated carcinogenesis, the roles of Hh signaling in tumor development and metastasis, antagonists for Hh signaling and their clinical implications.     

Targeting the Hedgehog pathway in cancer

The Hedgehog (Hh) pathway is a major regulator of many fundamental processes in vertebrate embryonic development including stem cell maintenance, cell differentiation, tissue polarity and cell proliferation. Constitutive activation of the Hh pathway leading to tumorigenesis is seen in basal cell carcinomas and medulloblastoma. A variety of other human cancers, including brain, gastrointestinal, lung, breast and prostate cancers, also demonstrate inappropriate activation of this pathway. Paracrine Hh signaling from the tumor to the surrounding stroma was recently shown to promote tumorigenesis. This pathway has also been shown to regulate proliferation of cancer stem cells and to increase tumor invasiveness. Targeted inhibition of Hh signaling may be effective in the treatment and prevention of many types of human cancers. The discovery and synthesis of specific Hh pathway inhibitors have significant clinical implications in novel cancer therapeutics. Several synthetic Hh antagonists are now available, several of which are undergoing clinical evaluation. The orally available compound, GDC-0449, is the farthest along in clinical development. Initial clinical trials in basal cell carcinoma and treatment of select patients with medulloblastoma have shown good efficacy and safety. We review the molecular basis of Hh signaling, the current understanding of pathway activation in different types of human cancers and we discuss the clinical development of Hh pathway inhibitors in human cancer therapy.     

Hedgehog-interacting protein is highly expressed in endothelial cells but down-regulated during angiogenesis and in several human tumors

Background  

The Hedgehog (Hh) signaling pathway regulates a variety of developmental processes, including vasculogenesis, and can also induce the expression of pro-angiogenic factors in fibroblasts postnatally. Misregulation of the Hh pathway has been implicated in a variety of different types of cancer, including pancreatic and small-cell lung cancer. Recently a putative antagonist of the pathway, Hedgehog-interacting protein (HIP), was identified as a Hh binding protein that is also a target of Hh signaling. We sought to clarify possible roles for HIP in angiogenesis and cancer.     

Hedgehog信号通路与肿瘤的关系

 Hedgehog(Hh)信号通路在脊椎动物胚胎发育过程中起核心作用,参与调控多个基本生命过程,包括细胞增殖、分化和组织塑形。在正常成人该通路涉及干细胞维持、组织修复和再生等过程。目前越来越多的证据表明Hh信号通路与人类肿瘤的增殖、生存能力等有相关性。     

Molecular pathways: the hedgehog signaling pathway in cancer

The Hedgehog (Hh) signaling pathway regulates embryonic development and may be aberrantly activated in a wide variety of human cancers. Efforts to target pathogenic Hh signaling have steadily progressed from the laboratory to the clinic, and the recent approval of the Hh pathway inhibitor vismodegib for patients with advanced basal cell carcinoma represents an important milestone. On the other hand, Hh pathway antagonists have failed to show significant clinical activity in other solid tumors. The reasons for these negative results are not precisely understood, but it is possible that the impact of Hh pathway inhibition has not been adequately measured by the clinical endpoints used thus far or that aberrancies in Hh signal transduction limits the activity of currently available pathway antagonists. Further basic and correlative studies to better understand Hh signaling in human tumors and validate putative antitumor mechanisms in the clinical setting may ultimately improve the success of Hh pathway inhibition to other tumor types. Clin Cancer Res; 18(18); 4883-8. ?2012 AACR.     

Hedgehog signaling pathway as a therapeutic target in various types of cancer

Hedgehog (Hh) signaling is an important factor in growth and patterning during embryonic development. A mutation in Patched, Smoothened or Gli1, which regulate the Hh signaling pathway, might lead to the onset of glioblastoma, basal cell carcinoma, medulloblastoma and rhabdomyosarcoma. Recently, Hh signaling has been reported to be activated in a ligand-dependent manner, contributing to carcinogenesis and cancer progression. Hedgehog signaling is reactivated in various types of cancer, and this contributes to cancer progression by facilitating proliferation, invasion and cell survival. Moreover, Hh signaling is associated with several other signaling pathways that contribute to cancer progression. These observations indicate that controlling Hh signaling might become a target for novel molecular targeting therapy.