Department of Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Drug Discovery & Biomedical Sciences, College of Pharmacy, The University of South Carolina, Columbia, SC 29208, USA.
Genes (Basel). 2021 May 30;12(6):845. doi: 10.3390/genes12060845.
ATM is among of the most critical initiators and coordinators of the DNA-damage response. ATM canonical and non-canonical signaling pathways involve hundreds of downstream targets that control many important cellular processes such as DNA damage repair, apoptosis, cell cycle arrest, metabolism, proliferation, oxidative sensing, among others. Of note, ATM is often considered a major tumor suppressor because of its ability to induce apoptosis and cell cycle arrest. However, in some advanced stage tumor cells, ATM signaling is increased and confers remarkable advantages for cancer cell survival, resistance to radiation and chemotherapy, biosynthesis, proliferation, and metastasis. This review focuses on addressing major characteristics, signaling pathways and especially the diverse roles of ATM in cellular homeostasis and cancer development.
ATM 是 DNA 损伤反应的最重要的启动子和协调子之一。ATM 的经典和非经典信号通路涉及数百个下游靶标，这些靶标控制着许多重要的细胞过程，如 DNA 损伤修复、细胞凋亡、细胞周期停滞、代谢、增殖、氧化感应等。值得注意的是，ATM 通常被认为是一种主要的肿瘤抑制因子，因为它能够诱导细胞凋亡和细胞周期停滞。然而，在一些晚期肿瘤细胞中，ATM 信号通路增强，并赋予癌细胞存活、抵抗放疗和化疗、生物合成、增殖和转移的显著优势。本综述重点讨论了 ATM 在细胞内稳态和癌症发展中的主要特征、信号通路，尤其是其多样化的作用。
