Mechanisms by which IGF-I May Promote Cancer
Mechanisms by which IGF-I May Promote Cancer
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DOI：
10.4161/cbt.2.6.678
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发表时间：
2003-11
影响因子：
3.6
通讯作者：
A. Grimberg
中科院分区：
文献类型：
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作者：
A. Grimberg
过去五年中的多项大型病例对照研究报告了胰岛素样生长因子 (IGF)-I 的高循环水平与不同类型癌症的风险之间存在正相关。相关性当然不能证明因果关系，但这一发现的可重复性意味着这是一个值得通过更多机制研究进一步检验的假设。 IGF-I 与 IGF-I 受体结合，IGF-I 受体是一种酪氨酸激酶受体，主要通过丝裂原激活蛋白激酶 (MAPK) 和 PI3K/Akt 途径将信号转导至细胞核和线粒体。将提供示例来说明 IGF-I 信号传导如何促进癌症进展的每个阶段：恶性转化、肿瘤生长、局部侵袭和远处转移以及对治疗的抵抗。除了对每个阶段的直接贡献外，IGF-I 还可能通过与癌基因和肿瘤抑制因子的相互作用、与其他激素（尤其是乳腺癌和前列腺癌中的性类固醇）的相互作用以及与 IGF 结合蛋白 (IGFBP) 的相互作用来间接促进癌症。最后，循环中的 IGF-I 可能会促进癌症的发展，尽管它可能不会导致癌症的形成。在越来越多的证据的推动下，人们也在进行研究以调节 IGF 系统作为癌症预防或治疗的可能手段。
Multiple large case-control studies in the past five years have reported positive associations between high circulating levels of the insulin-like growth factor (IGF)-I and risk for different types of cancer. Correlations certainly do not prove causation, but the reproducibility of this finding implies this is a hypothesis worth further examination through more mechanistic studies. IGF-I binds to the IGF-I receptor, a tyrosine kinase receptor that transduces signals to the nucleus and mitochondrion primarily via the mitogen-activated protein kinase (MAPK) and PI3K/Akt pathways. Examples will be provided to illustrate how IGF-I signaling may contribute to each stage of cancer progression: malignant transformation, tumor growth, local invasion and distant metastases, and resistance to treatment. In addition to direct contributions to each of these stages, IGF-I may promote cancer indirectly, through interactions with oncogenes and tumor suppressors, interactions with other hormones (especially the sex steroids in breast and prostate cancers) and interactions with the IGF binding proteins (IGFBPs). Finally, circulating IGF-I may facilitate cancer development though it likely does not cause cancer to form. Prompted by the accumulating evidence, investigations are also being pursued to modulate the IGF system as a possible means of cancer prevention or treatment.