Durzyńska Julia
Department of Molecular Virology, Institute of Experimental Biology, Faculty of Biology, Adam Mickiewicz University, 60-614 Poznań, Poland.
Oncol Rep. 2014 Dec;32(6):2295-306. doi: 10.3892/or.2014.3505. Epub 2014 Sep 19.
The insulin-like growth factor (IGF) axis promotes the growth of cells, tissues and organs. IGF-1 is mainly produced in the liver but is also secreted from local tissues. In the circulation, IGF-1 is bound to insulin-like binding proteins (IGFBPs), and when released it activates the insulin-like growth factor receptor (IGF-1R). The signal is further transmitted by intracellular signaling pathways leading to gene expression that regulates, among others, cell proliferation and survival. This review presents the IGF axis in the context of cell transformation and cancer development. Aspects involving IGF-1 deficiency and protection from cancer are also briefly described. Furthermore, human papillomaviruses (HPVs) interplaying with IGF axis components in cervical cancer development are described. These small dsDNA viruses are divided into low-risk and high-risk HPVs with regard to the potency of their oncogenic actions; they mainly infect epithelial or mucosal cells. Special attention is drawn to expression of two major HPV oncogenes (E6 and E7) initiating and maintaining cervical carcinogenesis, which is a multistep and multifactorial process; therefore, involvement of additional factors such as mitochondrial DNA changes, sex hormones, retinoic and folic acids are also discussed. Finally, IGF axis components and HPV oncogenes as targets in anticancer treatment are presented which include IGF-1R downregulation, RNA interference and anti-HPV therapeutic vaccines. The review concludes that despite an enormous advancement in research on IGF and HPV-related cancers, more molecular studies and clinical trials are needed before commercialized therapies are widely available for oncology patients.
胰岛素样生长因子（IGF）轴促进细胞、组织和器官的生长。IGF-1主要在肝脏中产生，但也从局部组织分泌。在循环中，IGF-1与胰岛素样结合蛋白（IGFBPs）结合，释放时激活胰岛素样生长因子受体（IGF-1R）。信号通过细胞内信号通路进一步传递，导致基因表达，进而调节细胞增殖和存活等过程。本综述在细胞转化和癌症发展的背景下介绍了IGF轴。还简要描述了与IGF-1缺乏和癌症预防相关的方面。此外，还描述了人乳头瘤病毒（HPV）在宫颈癌发展过程中与IGF轴成分的相互作用。这些小型双链DNA病毒根据其致癌作用的强度分为低风险和高风险HPV；它们主要感染上皮细胞或粘膜细胞。特别关注启动和维持宫颈癌发生的两个主要HPV癌基因（E6和E7）的表达，宫颈癌发生是一个多步骤、多因素的过程；因此，还讨论了线粒体DNA变化、性激素、视黄酸和叶酸等其他因素的参与。最后，介绍了作为抗癌治疗靶点的IGF轴成分和HPV癌基因，包括IGF-1R下调、RNA干扰和抗HPV治疗性疫苗。综述得出结论，尽管在IGF和HPV相关癌症的研究方面取得了巨大进展，但在商业化疗法广泛应用于肿瘤患者之前，仍需要更多的分子研究和临床试验。
