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通过雷帕霉素作用机制对干细胞进行引导。

Stem cell guidance through the mechanistic target of rapamycin.

作者信息

Maiese Kenneth

机构信息

Kenneth Maiese, Cellular and Molecular Signaling, Newark, NJ 07101, United States.

出版信息

World J Stem Cells. 2015 Aug 26;7(7):999-1009. doi: 10.4252/wjsc.v7.i7.999.

Abstract

Stem cells offer great promise for the treatment of multiple disorders throughout the body. Critical to this premise is the ability to govern stem cell pluripotency, proliferation, and differentiation. The mechanistic target of rapamycin (mTOR), 289-kDa serine/threonine protein kinase, that is a vital component of mTOR Complex 1 and mTOR Complex 2 represents a critical pathway for the oversight of stem cell maintenance. mTOR can control the programmed cell death pathways of autophagy and apoptosis that can yield variable outcomes in stem cell survival and be reliant upon proliferative pathways that include Wnt signaling, Wnt1 inducible signaling pathway protein 1 (WISP1), silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), and trophic factors. mTOR also is a necessary component for the early development and establishment of stem cells as well as having a significant impact in the regulation of the maturation of specific cell phenotypes. Yet, as a proliferative agent, mTOR can not only foster cancer stem cell development and tumorigenesis, but also mediate cell senescence under certain conditions to limit invasive cancer growth. mTOR offers an exciting target for the oversight of stem cell therapies but requires careful consideration of the diverse clinical outcomes that can be fueled by mTOR signaling pathways.

摘要

干细胞为治疗全身多种疾病带来了巨大希望。实现这一前提的关键在于控制干细胞多能性、增殖和分化的能力。雷帕霉素的机制靶点(mTOR)是一种289 kDa的丝氨酸/苏氨酸蛋白激酶,是mTOR复合物1和mTOR复合物2的重要组成部分,代表了监督干细胞维持的关键途径。mTOR可以控制自噬和凋亡的程序性细胞死亡途径,这些途径在干细胞存活中可能产生不同的结果,并且依赖于包括Wnt信号、Wnt1诱导信号通路蛋白1(WISP1)、沉默交配型信息调节2同源物1(酿酒酵母)(SIRT1)和营养因子在内的增殖途径。mTOR也是干细胞早期发育和建立的必要组成部分,并且在特定细胞表型成熟的调节中具有重要影响。然而,作为一种增殖剂,mTOR不仅可以促进癌症干细胞的发育和肿瘤发生,而且在某些条件下还可以介导细胞衰老以限制侵袭性癌症的生长。mTOR为监督干细胞治疗提供了一个令人兴奋的靶点,但需要仔细考虑mTOR信号通路可能引发的各种临床结果。

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