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

Yang, Haitang; Yao, Feng; Marti, Thomas M.; Schmid, Ralph A.; Peng, Ren-Wang (2020). Beyond DNA Repair: DNA-PKcs in Tumor Metastasis, Metabolism and Immunity. Cancers, 12(11) MDPI AG 10.3390/cancers12113389

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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.

Item Type:

Journal Article (Review Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Thoraxchirurgie

UniBE Contributor:

Yang, Haitang; Marti, Thomas; Schmid, Ralph and Peng, Ren-Wang

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2072-6694

Publisher:

MDPI AG

Language:

English

Submitter:

Thomas Michael Marti

Date Deposited:

05 Jan 2021 10:51

Last Modified:

05 Jan 2021 11:01

Publisher DOI:

10.3390/cancers12113389

PubMed ID:

33207636

Uncontrolled Keywords:

DNA damage response DNA-dependent protein kinase catalytic subunit biomarker immunity immunotherapy metabolism metastasis targeted therapy

BORIS DOI:

10.48350/150024

URI:

https://boris.unibe.ch/id/eprint/150024

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