The Role of Oxidative Stress in Tumorigenesis and Progression

Abstract

Oxidative stress refers to the imbalance between the production of reactive oxygen species (ROS) and the endogenous antioxidant defense system. Its involvement in cell senescence, apoptosis, and series diseases has been demonstrated. Advances in carcinogenic research have revealed oxidative stress as a pivotal pathophysiological pathway in tumorigenesis and to be involved in lung cancer, glioma, hepatocellular carcinoma, leukemia, and so on. This review combs the effects of oxidative stress on tumorigenesis on each phase and cell fate determination, and three features are discussed. Oxidative stress takes part in the processes ranging from tumorigenesis to tumor death via series pathways and processes like mitochondrial stress, endoplasmic reticulum stress, and ferroptosis. It can affect cell fate by engaging in the complex relationships between senescence, death, and cancer. The influence of oxidative stress on tumorigenesis and progression is a multi-stage interlaced process that includes two aspects of promotion and inhibition, with mitochondria as the core of regulation. A deeper and more comprehensive understanding of the effects of oxidative stress on tumorigenesis is conducive to exploring more tumor therapies.

Keywords: cell aging; cell death; mitochondria; oxidative stress; tumor treatment; tumorigenesis.

Figure 1

Oxidative stress plays a pivotal role in tumorigenesis. (Created with BioRender.com).

Figure 2

Oxidative stress based on ROS levels will directly affect tumor cell growth state. (Created with BioRender.com).

Figure 3

Oxidative stress is involved in tumor immunity. MDSCs, myeloid-derived suppressor cells; Tregs, regulatory T cells; TAMs, tumor-associated macrophages; CTL, cytotoxic T lymphocyte; TSTR, T cell stress response state; ILC, innate lymphoid cell. (Created with BioRender.com).

Figure 4

Four primary forms of tumor cell death and regulation of oxidative stress. MDM2, a p53-specific E3 ubiquitin ligase, as a potential target for activating p53 function in cancer therapy, mediates p53 degradation while responding to oxidative stress via being phosphorylated by AKT, ATM, and c-Abl under the state of oxidative stress [145,147]. SIRT1 and SIRT3, as stress responders, deacetylate and inhibit p53, inducing apoptosis in HCC [148,149]. (Created with BioRender.com).

Figure 5

Oxidative stress is involved in all phases of tumorigenesis. RAS: HRAS, NRAS, and KRAS; CTCL: cutaneous T-cell lymphoma; γδ T: γδ T cells. (Created with BioRender.com).

Figure 6

Oxidative stress plays a pivotal role in cell fate determination. (Created with BioRender.com).