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Review

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

1
Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China
2
Division of General Thoracic Surgery, Inselspital, Bern University Hospital, CH3008 Bern, Switzerland
3
Department of BioMedical Research (DBMR), University of Bern, 3012 Bern, Switzerland
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(11), 3389; https://doi.org/10.3390/cancers12113389
Received: 19 October 2020 / Revised: 10 November 2020 / Accepted: 12 November 2020 / Published: 16 November 2020
(This article belongs to the Special Issue DNA Damage and Repair in Cancers)
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has recently attracted increasing attention due to the emerging novel functions in cancer. However, several fundamental questions, such as the underlying molecular basis for DNA-PKcs pleiotropy and biomarkers for DNA-PKcs inhibitor sensitivity, remain to be addressed. In this review, we elaborate an updated summary of the most recent progress in DNA-PKcs, with particular emphasis on the mechanisms of DNA-PKcs multifaceted roles in malignancy and potential stratification approaches towards DNA-PKcs-based precision cancer therapy.
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. View Full-Text
Keywords: DNA-dependent protein kinase catalytic subunit; DNA damage response; metastasis; metabolism; immunity; biomarker; targeted therapy; immunotherapy DNA-dependent protein kinase catalytic subunit; DNA damage response; metastasis; metabolism; immunity; biomarker; targeted therapy; immunotherapy
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MDPI and ACS Style

Yang, H.; Yao, F.; Marti, T.M.; Schmid, R.A.; Peng, R.-W. Beyond DNA Repair: DNA-PKcs in Tumor Metastasis, Metabolism and Immunity. Cancers 2020, 12, 3389. https://doi.org/10.3390/cancers12113389

AMA Style

Yang H, Yao F, Marti TM, Schmid RA, Peng R-W. Beyond DNA Repair: DNA-PKcs in Tumor Metastasis, Metabolism and Immunity. Cancers. 2020; 12(11):3389. https://doi.org/10.3390/cancers12113389

Chicago/Turabian Style

Yang, Haitang, Feng Yao, Thomas M. Marti, Ralph A. Schmid, and Ren-Wang Peng. 2020. "Beyond DNA Repair: DNA-PKcs in Tumor Metastasis, Metabolism and Immunity" Cancers 12, no. 11: 3389. https://doi.org/10.3390/cancers12113389

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