Interplay between heat shock proteins, inflammation and cancer: a potential cancer therapeutic target

American Journal of Cancer Research

Paul C Ikwegbue¹  Priscilla Masamba² 

[1] Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa;Department of Biochemistry, College of Sciences, Afe Babalola University, Ado-Ekiti 36000, Ekiti, Nigeria, Africa

关键词: Heat shock proteins;    inflammation;    cancer;    DNA damage response;    5-chlorocytosine;    hypochlorous acid;   

DOI  :  

学科分类：肿瘤学

来源: e-Century Publishing Corporation

【 摘 要 】

The historical relationship between cancer and inflammation has long been evaluated, and dates back to the early work of Virchow (1863), where he hypothesised that chronic inflammation as a direct cause of tissue injury and infection, could actually promote tissue proliferation. At that period in time however, the exact mechanisms that mediated this relationship were little understood. Subsequent studies have since then demonstrated that chronic inflammation plays significant roles in microenvironments, mostly in the progression of tumours, probably, through over-secretion of proinflammatory cytokines and other immune-killing apparatus such as reactive oxygen species (ROS) which cause damage to normal cells leading to DNA damage and increased cellular mutation rates. Recently, the identification of DNA lesion 5-chlorocytosine (5-CIC) created by hypochlorous acid (HOCl) secreted to nullify or kill infectious agents and toll-like receptor 4 (TLR4)-mediated chronic inflammation in the human gut, has become the latest evidence linking inflammation directly to cancer. The key to cellular survival and adaptation under unfavourable or pathological conditions is the expression of heat shock proteins (HSPs) also called molecular chaperones. These proteins play essential roles in DNA repair processes by maintaining membrane integrity, orderliness and stability of client proteins that play prominent roles in DNA repair mechanisms. More so, HSPs have also been shown to modulate the effects of pro-inflammatory/apoptotic cytokines through the inhibition of cascades leading to the generation of ROS-mediated DNA damage, while promoting the DNA repair mechanism, thus playing prominent roles in various stages of DNA repair and cancer progression. Hence, studies targeting HSPs and their inhibitors in inflammation, DNA damage, and repair, could improve current cancer therapeutic efficiency. Here the focus will be on the relationship between HSPs, inflammation and cancer, as well as roles of HSPs in DNA damage response (DDR).

【 授权许可】

CC BY-NC