Shh信号通路在神经胶质瘤发生发展中的作用

Sonic hedgehog signaling pathway in tumorigenesis of glioma

Sonic hedgehog(Shh)信号转导通路是脊椎动物hedgehog信号通路家族成员之一,主要由分泌型糖蛋白Shh配体、跨膜蛋白受体Ptch和Smo以及下游转录因子Gli蛋白组成,在胚胎发育尤其是神经系统发育中起着重要的作用。近年研究发现Shh信号通路与多种肿瘤的形成有着密切的关系。神经胶质瘤是最常见的原发性脑肿瘤,生长迅速且多呈浸润性,易复发,是脑肿瘤中治疗效果最差的肿瘤之一,主要原因是多种信号通路的异常激活增强了胶质瘤细胞的增殖能力。此外,神经胶质瘤是由不同属性的肿瘤细胞混合构成,胶质瘤中的肿瘤干细胞具有无限增殖能力,这一特性也对胶质瘤的发生、发展和复发起着重要作用。有研究发现Shh信号通路与神经胶质瘤的发生、增殖及胶质瘤干细胞有密切关系。本文主要就Shh信号通路的组成和其在神经胶质瘤发生及胶质瘤干细胞中的相关作用作一综述。

Sonic hedgehog（Shh） is a member of the hedgehog family in vertebrate.The Shh signaling pathway is mainly composed of a secreted glycoprotein,named Shh,two transmembrane proteins（Ptch and Smo） and the downstream transcription factor family Glis.It plays a vital role in the embryo development,especially in the neuronal system.Recent study have demonstrated that the Shh pathway is closely associated with the tumorigenesis of various tumors.Glioma,the most common malignant brain tumor of humans,is characterized by the rapid proliferation,infiltrative growth and high rate of relapse,and it is one of the brain tumors with poorest prognosis.Abnormal activation of multiple signaling pathways has been known to enhance the proliferation ability of glioma cells.Moreover,glioma is composed of various tumor cells and the glioma stem cells were endowed with the ability of self-renewal and unlimited proliferation,which plays a key role in the tumorigenesis,progress and relapse.Evidence has been found that Shh signaling pathway is closely assoicated with tumorigenesis of glioma.Herein we review the current knowledge on the components of Shh signaling pathway and its role in the tumorigenesis of glioma and glioma stem cells.