Department of Pharmaco-Biology, University of Calabria, 87030 Rende, Italy.
Cell Signal. 2012 Aug;24(8):1515-21. doi: 10.1016/j.cellsig.2012.03.012. Epub 2012 Mar 28.
There is increasing awareness that estrogens may affect cell functions through the integration with a network of signaling pathways. The IGF system is a phylogenetically highly conserved axis that includes the insulin receptor (IR) and the insulin-like growth factor I receptor (IGF-IR) pathways, which are of crucial importance in the regulation of metabolism and cell growth in relationship to nutrient availability. Numerous studies nowadays document that estrogens cooperate with IGF system at multiple levels both in physiology and in disease. Several studies have focused on this bidirectional cross-talk in central nervous system, in mammary gland development and in cancer. Notably, cancer cells show frequent deregulation of the IGF system with overexpression of IR and/or IGF-IR and their ligands as well as frequent upregulation of the classical estrogen receptor (ER)α and the novel ER named GPER. Recent studies have, therefore, unraveled further mechanisms of cross-talk involving membrane initiated estrogen actions and the IGF system in cancer, that converge in the stimulation of pro-tumoral effects. These studies offer hope for new strategies aimed at the treatment of estrogen related cancers in order to prevent an estrogen-independent and more aggressive tumor progression.
人们越来越意识到，雌激素可能通过与信号通路网络的整合来影响细胞功能。IGF 系统是一个在进化上高度保守的轴，包括胰岛素受体 (IR) 和胰岛素样生长因子 I 受体 (IGF-IR) 途径，这些途径在调节与营养供应有关的代谢和细胞生长方面至关重要。如今，许多研究都证明，雌激素在生理和疾病方面在多个层面上与 IGF 系统相互作用。一些研究集中在中枢神经系统、乳腺发育和癌症中的这种双向串扰上。值得注意的是，癌细胞经常出现 IGF 系统的失调，表现为 IR 和/或 IGF-IR 及其配体的过度表达，以及经典雌激素受体 (ER)α 和新型 ER 即 GPER 的频繁上调。最近的研究揭示了涉及膜起始雌激素作用和 IGF 系统的癌症中相互作用的进一步机制，这些机制集中在促进促肿瘤效应上。这些研究为旨在治疗与雌激素相关的癌症以防止雌激素非依赖性和更具侵袭性的肿瘤进展的新策略提供了希望。
