Camfield Sydney, Chakraborty Sayan, Dwivedi Shailendra Kumar Dhar, Pramanik Pijush Kanti, Mukherjee Priyabrata, Bhattacharya Resham
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
NPJ Precis Oncol. 2024 Jul 23;8(1):154. doi: 10.1038/s41698-024-00655-1.
The canonical role of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in repairing DNA double-strand breaks combined with its reported dysregulation in several malignancies has driven the development of DNA-PKcs inhibitors as therapeutics. However, until recently the relationship between DNA-PKcs and tumorigenesis has been primarily investigated with regard to its role in non-homologous end joining (NHEJ) repair. Emerging research has uncovered non-canonical DNA-PKcs functions involved with transcriptional regulation, telomere maintenance, metabolic regulation, and immune signaling all of which may also impinge on tumorigenesis. This review mainly discusses these non-canonical roles of DNA-PKcs in cellular biology and their potential contribution to tumorigenesis, as well as evaluating the implications of targeting DNA-PKcs for cancer therapy.
DNA依赖蛋白激酶催化亚基（DNA-PKcs）在修复DNA双链断裂中的经典作用，及其在多种恶性肿瘤中报道的失调现象，推动了DNA-PKcs抑制剂作为治疗药物的开发。然而，直到最近，DNA-PKcs与肿瘤发生之间的关系主要是在其非同源末端连接（NHEJ）修复作用方面进行研究。新兴研究发现了DNA-PKcs的非经典功能，涉及转录调控、端粒维持、代谢调节和免疫信号传导，所有这些都可能影响肿瘤发生。本综述主要讨论DNA-PKcs在细胞生物学中的这些非经典作用及其对肿瘤发生的潜在贡献，同时评估靶向DNA-PKcs进行癌症治疗的意义。
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