Beyond DNA Repair: DNA-PKcs in Tumor Metastasis, Metabolism and Immunity

• Main Authors: Haitang Yang, Feng Yao, Thomas M. Marti, Ralph A. Schmid, Ren-Wang Peng
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: Cancers
• Subjects: DNA-dependent protein kinase catalytic subunit; DNA damage response; metastasis; metabolism; immunity; biomarker
• Online Access: https://www.mdpi.com/2072-6694/12/11/3389

The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a key component of the DNA-PK complex that has a well-characterized function in the non-homologous end-joining repair of DNA double-strand breaks. Since its identification, a large body of evidence has demonstrated that DNA-PKcs is frequently overexpressed in cancer, plays a critical role in tumor development and progression, and is associated with poor prognosis of cancer patients. Intriguingly, recent studies have suggested novel functions beyond the canonical role of DNA-PKcs, which has transformed the paradigm of DNA-PKcs in tumorigenesis and has reinvigorated the interest to target DNA-PKcs for cancer treatment. In this review, we update recent advances in DNA-PKcs, in particular the emerging roles in tumor metastasis, metabolic dysregulation, and immune escape. We further discuss the possible molecular basis that underpins the pleiotropism of DNA-PKcs in cancer. Finally, we outline the biomarkers that may predict the therapeutic response to DNA-PKcs inhibitor therapy. Understanding the functional repertoire of DNA-PKcs will provide mechanistic insights of DNA-PKcs in malignancy and, more importantly, may revolutionize the design and utility of DNA-PKcs-based precision cancer therapy.