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Wang et al. J Cancer Metastasis Treat 2017;3:45-59 Journal of
DOI: 10.20517/2394-4722.2017.03
Cancer Metastasis and Treatment

www.jcmtjournal.com
Review Open Access

DNA damage-induced nuclear factor-kappa B

activation and its roles in cancer progression

Wei Wang , Arul M. Mani , Zhao-Hui Wu 1, 2
1, 2
1, 2
1 Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
2 Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

Correspondence to: Dr. Zhao-Hui Wu, Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center,
Memphis, TN 38163, USA. E-mail: zwu6@uthsc.edu
How to cite this article: Wang W, Mani AM, Wu ZH. DNA damage-induced nuclear factor-kappa B activation and its roles in cancer progression. J
Cancer Metastasis Treat 2017;3:45-59.

Dr. Zhao-Hui Wu is an Associate Professor in the Department of Pathology and Laboratory Medicine at the
University of Tennessee Health Science Center. The research in his lab focuses on exploring the mechanisms
involved in the acquired and innate therapeutic resistance of cancer cells. Through delineating the molecular
and cellular signaling pathway exploited by tumor cells to evade the elimination by anti-cancer drugs, they are
aiming to screen potential novel drug targeting these pathways to improve the therapeutic efficacy of cancer
treatments.

ABSTRACT
Article history: DNA damage is a vital challenge to cell homeostasis. Cellular responses to DNA damage
Received: 05-01-2017 (DDR) play essential roles in maintaining genomic stability and survival, whose failure
Accepted: 02-03-2017 could lead to detrimental consequences such as cancer development and aging. Nuclear
Published: 27-03-2017 factor-kappa B (NF-kB) is a family of transcription factors that plays critical roles in
cellular stress response. Along with p53, NF-kB modulates transactivation of a large
Key words: number of genes which participate in various cellular processes involved in DDR. Here the
DNA damage, authors summarize the recent progress in understanding DNA damage response and NF-
nuclear factor-kappa B, kB signaling pathways. This study particularly focuses on DNA damage-induced NF-kB
signal transduction, signaling cascade and its physiological and pathological significance in B cell development
metastasis, and cancer therapeutic resistance. The authors also discuss promising strategies for
therapeutic resistance selectively targeting this genotoxic NF-kB signaling aiming to antagonize acquired
resistance and resensitize refractory cancer cells to cytotoxic treatments.

INTRODUCTION threatened by a variety of agents which cause DNA
damage. DNA lesions may occur by altering DNA
The genome of all living organisms is constantly bases (i.e. O -methylguanine and thymine glycols),
6

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