文章：

成纤维细胞生长因子信号传导：从发育到癌症

Fibroblast growth factor signalling: from development to cancer

原文发布日期：2010-02-01

DOI: 10.1038/nrc2780

类型: Review Article

开放获取: 否

要点：

1. Fibroblast growth factors (FGFs) and their receptors (FGFRs) drive crucial developmental signalling pathways, which are responsible for many functions, including cell proliferation, survival and migration. As such, they are susceptible to hijack by cancer cells and have been shown to have oncogenic roles in many cancers.
2. Conversely, FGFR signalling can also have tumour suppressive roles, through driving differentiation, regulating other oncogenic pathways, protecting cells from damage or perhaps by mediating immune surveillance.
3. The specific cellular context in which FGF signalling occurs is clearly important for determining whether oncogenic or tumour protective outcomes are evoked, and understanding more about context-specific FGF signalling is a key area of research.
4. There are several types of genetic evidence that support an oncogenic function for FGFRs: identification of gene amplifications, activating mutations, chromosomal translocations, single nucleotide polymorphisms and aberrant splicing at the post-transcriptional level. Expression of FGFs can also be affected by gene amplification.
5. There is now evidence from multiple cancer types to implicate FGF signalling in several oncogenic behaviours, including proliferation, survival, migration, invasion and angiogenesis.
6. Therapeutic targeting of FGFs and their receptors is a major area of drug development research. Most agents are small-molecule tyrosine kinase inhibitors, but blocking antibodies and ligand-trap approaches are also being developed.

要点翻译：

1. 成纤维细胞生长因子（FGFs）及其受体（FGFRs）驱动关键的发育信号通路，这些通路负责多种功能，包括细胞增殖、存活与迁移。因此，它们易被癌细胞劫持，并已被证实在多种癌症中具有致癌作用。
2. 相反地，FGFR信号传导亦可通过驱动分化、调节其他致癌通路、保护细胞免受损伤或通过介导免疫监视等方式发挥肿瘤抑制作用。
3. FGF信号传导所处的特定细胞环境显然对决定其诱发致癌效应还是肿瘤保护效应至关重要，而深入了解环境特异性FGF信号传导是当前研究的重点领域。
4. 多种遗传学证据支持FGFRs的致癌功能：包括基因扩增的识别、激活突变、染色体易位、单核苷酸多态性以及转录后水平的异常剪接。FGFs的表达同样可能受基因扩增影响。
5. 现有来自多种癌症类型的证据表明，FGF信号传导与多种致癌行为相关，包括增殖、存活、迁移、侵袭和血管生成。
6. 针对FGFs及其受体的治疗靶向研究是药物开发的重要领域。目前多数药物为小分子酪氨酸激酶抑制剂，但阻断抗体和配体捕获方法也正在研发中。

英文摘要：

Fibroblast growth factors (FGFs) and their receptors control a wide range of biological functions, regulating cellular proliferation, survival, migration and differentiation. Although targeting FGF signalling as a cancer therapeutic target has lagged behind that of other receptor tyrosine kinases, there is now substantial evidence for the importance of FGF signalling in the pathogenesis of diverse tumour types, and clinical reagents that specifically target the FGFs or FGF receptors are being developed. Although FGF signalling can drive tumorigenesis, in different contexts FGF signalling can mediate tumour protective functions; the identification of the mechanisms that underlie these differential effects will be important to understand how FGF signalling can be most appropriately therapeutically targeted.

摘要翻译： 

成纤维细胞生长因子（FGF）及其受体调控着广泛的生物学功能，包括细胞增殖、存活、迁移和分化。尽管靶向FGF信号通路作为癌症治疗策略的研究进展落后于其他受体酪氨酸激酶，但现有大量证据表明FGF信号在多种肿瘤类型的发病机制中具有重要作用，且针对FGF或FGF受体的特异性临床试剂正在开发中。尽管FGF信号可促进肿瘤发生，但在不同背景下其亦可发挥抑瘤功能；阐明这些差异效应背后的机制对于理解如何最恰当地靶向FGF信号通路至关重要。

原文链接：

Fibroblast growth factor signalling: from development to cancer