Stem cell quiescence.
Stem cell quiescence.
复制标题
DOI：
10.1158/1078-0432.ccr-10-1499
复制
发表时间：
2011-08-01
期刊：
影响因子：
--
通讯作者：
Bhatia R
中科院分区：
文献类型：
--
作者：
Li L;Bhatia R
成体干细胞维持在静止状态，但能够退出静止，并在应激反应中迅速扩增和分化。静止状态似乎是保持干细胞自我更新所必需的，也是癌症干细胞（CSC）对化疗和靶向治疗抵抗的关键因素。对静止机制的有限了解阻碍了临床中靶向耐药静止CSC群体的重大进展。因此，提高对成体干细胞中静止的分子机制的理解对于开发针对不同癌症中静止CSC的分子靶向疗法至关重要。最近的研究提供了一个更好的理解内在和外在的调控机制，控制干细胞静止。现在认识到p53基因在调节干细胞静止中起关键作用。其他内在调节机制包括FoxO、HIF-1α和NFATc 1转录因子，以及通过ATM和mTOR的信号传导。外源性微环境调节机制包括血管生成素-1、TGF-β、BMP、TPO、N-钙粘蛋白和整合素粘附受体、Wnt/β-连环蛋白信号传导和骨桥蛋白。在这篇文章中，我们回顾了目前的进展，了解正常干细胞的静止，其意义CSC静止和耐药性，以及这些发现的潜在临床应用。
Adult stem cells are maintained in a quiescent state, but are able to exit quiescence and rapidly expand and differentiate in response to stress. The quiescent state appears to be necessary for preserving self-renewal of stem cells and a critical factor in resistance of cancer stem cells (CSC) to chemotherapy and targeted therapies. Limited knowledge of quiescence mechanisms has prevented significant advance in targeting of drug resistant quiescent CSC populations in the clinic. Thus improved understanding of the molecular mechanisms of quiescence in adult stem cells is critical for development of molecularly targeted therapies against quiescent CSC in different cancers. Recent studies have provided a better understanding of intrinsic and extrinsic regulatory mechanisms that control stem cell quiescence. It is now appreciated that the p53 gene plays a critical role in regulating stem cell quiescence. Other intrinsic regulatory mechanisms include the FoxO,, HIF-1α and NFATc1 transcription factors, and signaling through ATM and mTOR. Extrinsic microenvironmental regulatory mechanisms include Angiopoietin-1, TGF-β, BMP, TPO, N-Cadherin and integrin adhesion receptors, Wnt/β-catenin signaling and osteopontin. In this article, we review current advances in understanding normal stem cell quiescence, their significance for CSC quiescence and drug resistance, and the potential clinical applications of these findings.