Farooqi Ammad Ahmad, Attar Rukset, Arslan Belkis Atasever, Romero Mirna Azalea, ul Haq Muhammad Fahim, Qadir Muhammad Imran
Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore, Pakistan E-mail :
Asian Pac J Cancer Prev. 2014;15(16):6485-8. doi: 10.7314/apjcp.2014.15.16.6485.
Research over the years has progressively and sequentially provided near complete resolution of regulators of the DNA repair pathways which are so important for cancer prevention. Ataxia-telangiectasia mutated kinase (ATM), a high-molecular-weight PI3K-family kinase has emerged as a master regulator of DNA damage signaling and extensive cross-talk between ATM and downstream proteins forms an interlaced signaling network. There is rapidly growing scientific evidence emphasizing newly emerging paradigms in ATM biology. In this review, we provide latest information regarding how oxidative stress induced activation of ATM can be utilized as a therapeutic target in different cancer cell lines and in xenografted mice. Moreover, crosstalk between autophagy and ATM is also discussed with focus on how autophagy inhibition induces apoptosis in cancer cells.
多年来的研究逐步且相继地几乎完全解析了对癌症预防极为重要的DNA修复途径的调控因子。共济失调毛细血管扩张症突变激酶（ATM），一种高分子量的PI3K家族激酶，已成为DNA损伤信号传导的主要调控因子，并且ATM与下游蛋白之间广泛的相互作用形成了一个交错的信号网络。越来越多的科学证据强调了ATM生物学中新出现的范式。在本综述中，我们提供了有关如何将氧化应激诱导的ATM激活用作不同癌细胞系和异种移植小鼠中的治疗靶点的最新信息。此外，还讨论了自噬与ATM之间的相互作用，重点是自噬抑制如何诱导癌细胞凋亡。
