Abstract：
In proliferating cells and tissues a number of checkpoints (G1/S and G2/M) preceding cell division (M-phase) require the signal provided by growth factors present in serum. IGFs (I and II) have been demonstrated to constitute key intrinsic components of the peptidic active fraction of mammalian serum. In vivo genetic ablation studies have shown that the cellular signal triggered by the IGFs through their cellular receptors represents a non-replaceable requirement for cell growth and cell cycle progression. Retroactive and current evaluation of published literature sheds light on the intracellular circuitry activated by these factors providing us with a better picture of the pleiotropic mechanistic actions by which IGFs regulate both cell size and mitogenesis under developmental growth as well as in malignant proliferation. The present work aims to summarize the cumulative knowledge learned from the IGF ligands/receptors and their intracellular signaling transducers towards control of cell size and cell-cycle with particular focus to their actionable circuits in human cancer. Furthermore, we bring novel perspectives on key functional discriminants of the IGF growth-mitogenic pathway allowing re-evaluation on some of its signal components based upon established evidences.
摘要：
在增殖的细胞和组织中,细胞分裂(M期)之前的许多检查点(G1/S和G2/M)需要由血清中存在的生长因子提供的信号。已证明IGFs(I和II)构成哺乳动物血清的肽活性部分的关键内在组分。体内遗传消融研究表明，由IGF通过其细胞受体触发的细胞信号代表了细胞生长和细胞周期进程的不可替代要求。对已发表文献的回顾性和当前评估揭示了由这些因子激活的细胞内回路，为我们提供了更好的多效性机制作用的图片，通过该机制，IGF在发育生长以及恶性增殖中调节细胞大小和有丝分裂。本工作旨在总结从IGF配体/受体及其细胞内信号转导子中获得的累积知识，以控制细胞大小和细胞周期，特别关注其在人类癌症中的可操作回路。此外，我们为IGF生长-促有丝分裂途径的关键功能判别式带来了新的观点，从而可以根据已建立的证据对其某些信号成分进行重新评估。
