Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznań, Poland.
Department of Gynecological Oncology and Gynecology, Medical University of Lublin, Lublin 20-081, Poland.
Mutat Res Rev Mutat Res. 2017 Apr-Jun;772:78-104. doi: 10.1016/j.mrrev.2016.08.007. Epub 2016 Sep 4.
Determination of the role of insulin-like growth factor (IGF) family components in carcinogenesis of several human tumors is based on numerous epidemiological and pre-clinical studies, experiments in vivo and in vitro and on attempts at application of drugs affecting the IGF axis. Investigative hypotheses in original studies were based on biological functions manifested by the entire family of IGF (ligands, receptors, linking proteins, adaptor molecules). In the context of carcinogenesis the most important functions of IGF family involve intensification of proliferation and inhibition of cell apoptosis and effect on cell transformation through synthesis of several regulatory proteins. IGF axis controls survival and influences on metastases of cells. Interactions of IGF axis components may be of a direct or indirect nature. The direct effects are linked to activation of PI3K/Akt signaling pathway, in which the initiating role is first of all played by IGF-1 and IGF-1R. Activity of this signaling pathway leads to an increased mitogenesis, cell cycle progression, and protection against different apoptotic stresses. Indirect effects of the axis depend on interactions between IGF and other molecules important for cancer etiology (e.g. sex hormones, products of suppressor genes, viruses, and other GFs) and the style of life (nutrition, physical activity). From the clinical point of view, components of IGF system are first of all considered as diagnostic serous and/or tissue biomarkers of a given cancer, prognostic factors and attractive target of modern anti-tumor therapies. Several mechanisms in which IGF system components act in the process of carcinogenesis need to be clarified, mainly due to multifactorial etiology of the neoplasms. Pin-pointing of the role played in carcinogenesis by any single signaling pathway remains particularly difficult. The aim of this review is to summarize the current data of several epidemiological studies, experiments in vitro and on animal models, to increase our understanding of the complex role of IGF family components in the most common human cancers.
确定胰岛素样生长因子（IGF）家族成分在几种人类肿瘤发生中的作用是基于大量的流行病学和临床前研究、体内和体外实验以及尝试应用影响 IGF 轴的药物。原始研究中的研究假设基于整个 IGF 家族（配体、受体、连接蛋白、衔接分子）表现出的生物学功能。在肿瘤发生的背景下，IGF 家族最重要的功能涉及通过合成几种调节蛋白来增强增殖、抑制细胞凋亡和影响细胞转化。IGF 轴控制细胞的存活并影响转移。IGF 轴成分的相互作用可能具有直接或间接的性质。直接作用与 PI3K/Akt 信号通路的激活有关，在该信号通路中，IGF-1 和 IGF-1R 首先发挥启动作用。该信号通路的活性导致有丝分裂的增加、细胞周期的进展以及对不同凋亡应激的保护。轴的间接作用取决于 IGF 与其他对癌症病因学（例如性激素、抑癌基因产物、病毒和其他生长因子）重要的分子以及生活方式（营养、体育活动）之间的相互作用。从临床的角度来看，IGF 系统的成分首先被认为是特定癌症的血清和/或组织诊断生物标志物、预后因素和现代抗肿瘤治疗的有吸引力的靶点。需要阐明 IGF 系统成分在肿瘤发生过程中起作用的几个机制，主要是由于肿瘤的多因素病因。要确定任何单一信号通路在肿瘤发生中所起的作用仍然特别困难。本文的目的是总结几项流行病学研究、体外和动物模型实验的当前数据，以增加我们对 IGF 家族成分在最常见人类癌症中的复杂作用的理解。
