The emerging role of insulin and insulin-like growth factor signaling in cancer stem cells.
The emerging role of insulin and insulin-like growth factor signaling in cancer stem cells.
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DOI：
10.3389/fendo.2014.00010
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发表时间：
2014
影响因子：
5.2
通讯作者：
Belfiore A
中科院分区：
文献类型：
--
作者：
Malaguarnera R;Belfiore A
癌细胞经常利用IGF信号，这是一种调节发育、细胞生长和生存的基本途径。因此，IGF信号的几个组成部分在癌症中被解除调控，并维持癌症的进展。然而，IGF-IR在人类中的特异性靶向仅在一小部分癌症中有效，这使得研究人员怀疑IGF系统靶向是否仍然值得在临床环境中进行研究。尽管目前还没有确切的答案，但已经越来越清楚的是，IGF信号通路的其他成分，如IR-A，可能取代IGF-IR的缺乏，诱导肿瘤耐药和/或克隆选择。此外，现在越来越多的证据表明，IGF信号在诱导/维持上皮间充质转化(EMT)和细胞干性方面发挥着核心作用，这两个严格相关的程序在转移扩散和对癌症治疗的抵抗中发挥着关键作用。在这里，我们回顾了证据表明，IGF信号增强了EMT程序中涉及的转录因子的表达，并与参与细胞多能性和干性维持的特定通路有广泛的相互作用。反过来，EMT和细胞干性激活正反馈机制，导致各种IGF信号成分的上调。这些发现可能具有新的翻译含义。
Cancer cells frequently exploit the IGF signaling, a fundamental pathway mediating development, cell growth, and survival. As a consequence, several components of the IGF signaling are deregulated in cancer and sustain cancer progression. However, specific targeting of IGF-IR in humans has resulted efficacious only in small subsets of cancers, making researches wondering whether IGF system targeting is still worth pursuing in the clinical setting. Although no definite answer is yet available, it has become increasingly clear that other components of the IGF signaling pathway, such as IR-A, may substitute for the lack of IGF-IR, and induce cancer resistance and/or clonal selection. Moreover, accumulating evidence now indicates that IGF signaling is a central player in the induction/maintenance of epithelial mesenchymal transition (EMT) and cell stemness, two strictly related programs, which play a key role in metastatic spread and resistance to cancer treatments. Here we review the evidences indicating that IGF signaling enhances the expression of transcription factors implicated in the EMT program and has extensive cross-talk with specific pathways involved in cell pluripotency and stemness maintenance. In turn, EMT and cell stemness activate positive feed-back mechanisms causing up-regulation of various IGF signaling components. These findings may have novel translational implications.
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