The CCN proteins: important signaling mediators in stem cell differentiation and tumorigenesis.
The CCN proteins: important signaling mediators in stem cell differentiation and tumorigenesis.
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DOI：
10.14670/hh-25.795
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发表时间：
2010-06
影响因子：
2
通讯作者：
Luo Q
中科院分区：
文献类型：
--
作者：
Zuo GW;Kohls CD;He BC;Chen L;Zhang W;Shi Q;Zhang BQ;Kang Q;Luo J;Luo X;Wagner ER;Kim SH;Restegar F;Haydon RC;Deng ZL;Luu HH;He TC;Luo Q
CCN蛋白包含6个成员，即CCN1至CCN6，它们是富含半胱氨酸的小分泌蛋白。CCN蛋白是模块化蛋白，包含多达四个功能域。许多CCN成员是由生长因子、细胞因子或细胞应激诱导的。ccn在成人和胚胎组织中表现出广泛和高度可变的表达模式。CCN蛋白可以整合和调节整合素、bmp、VEGF、wnt和Notch的信号。整合素参与介导CCN信号传导可能在不同的细胞类型中提供不同的上下文依赖反应。CCN1和CCN2在发育、血管生成和细胞粘附中起重要作用，而CCN3在骨骼和心脏发育中起关键作用。CCN4、CCN5和CCN6通常抑制细胞生长。Ccn6突变与进行性假风湿性疾病样发育不良和迟发性脊柱骨骺发育不良有关。在干细胞分化过程中，CCN1、CCN2和CCN3在成骨、软骨和血管生成中起主要作用。CCN1的表达升高与人类癌症更具侵袭性的表型相关，而CCN2和CCN3在肿瘤发生中的作用是肿瘤类型依赖的。CCN4、CCN5和CCN6作为肿瘤抑制因子。虽然CCN蛋白可能在微调其他主要信号通路中发挥重要作用，但这些蛋白的确切功能和作用机制尚不清楚。了解CCN蛋白的生物学功能不仅可以深入了解它们在许多细胞过程中的作用，还可以为开发针对CCN功能的治疗方法提供机会。
The CCN proteins contain six members, namely CCN1 to CCN6, which are small secreted cysteine-rich proteins. The CCN proteins are modular proteins, containing up to four functional domains. Many of the CCN members are induced by growth factors, cytokines, or cellular stress. The CCNs show a wide and highly variable expression pattern in adult and in embryonic tissues. The CCN proteins can integrate and modulate the signals of integrins, BMPs, VEGF, Wnts, and Notch. The involvement of integrins in mediating CCN signaling may provide diverse context-dependent responses in distinct cell types. CCN1 and CCN2 play an important role in development, angiogenesis and cell adhesion, whereas CCN3 is critical to skeletal and cardiac development. CCN4, CCN5 and CCN6 usually inhibit cell growth. Mutations of Ccn6 are associated with the progressive pseudorheumatoid dysplasia and spondyloepiphyseal dysplasia tarda. In stem cell differentiation, CCN1, CCN2, and CCN3 play a principal role in osteogenesis, chondrogenesis, and angiogenesis. Elevated expression of CCN1 is associated with more aggressive phenotypes of human cancer, while the roles of CCN2 and CCN3 in tumorigenesis are tumor type-dependent. CCN4, CCN5 and CCN6 function as tumor suppressors. Although CCN proteins may play important roles in fine-tuning other major signaling pathways, the precise function and mechanism of action of these proteins remain undefined. Understanding of the biological functions of the CCN proteins would not only provide insight into their roles in numerous cellular processes but also offer opportunities for developing therapeutics by targeting CCN functions.