RAS/MAPK signaling functions in oxidative stress, DNA damage response and cancer progression

• Published in: Journal of cellular physiology 2019-09, Vol.234 (9), p.14951-14965
• Main Authors: Rezatabar, Setareh, Karimian, Ansar, Rameshknia, Vahid, Parsian, Hadi, Majidinia, Maryam, Kopi, Tayebeh Azramezani, Bishayee, Anupam, Sadeghinia, Ali, Yousefi, Mehdi, Monirialamdari, Mohsen, Yousefi, Bahman
• Format: Article
• Language: English
• Subjects: Apoptosis; Cancer; Carcinogenesis; Carcinogens; Cascades; Cell death; Cell division; Constitution; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; Energy metabolism; ERK; Extracellular signal-regulated kinase; Intracellular signalling; Kinases; MAP kinase; MAPK; Metabolic pathways; Metabolism; Mutation; Oxidative metabolism; Oxidative stress; Pathogenesis; Physiology; Protein kinase; Reactive oxygen species; Signal transduction; Tumor suppression
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.28334

Mitogen‐activated protein kinase (MAPK) signaling pathways organize a great constitution network that regulates several physiological processes, like cell growth, differentiation, and apoptotic cell death. Due to the crucial importance of this signaling pathway, dysregulation of the MAPK signaling cascades is involved in the pathogenesis of various human cancer types. Oxidative stress and DNA damage are two important factors which in common lead to carcinogenesis through dysregulation of this signaling pathway. Reactive oxygen species (ROS) are a common subproduct of oxidative energy metabolism and are considered to be a significant physiological modulator of several intracellular signaling pathways including the MAPK pathway. Studies demonstrated that the MAP kinases extracellular signal‐regulated kinase (ERK) 1/2 and p38 were activated in response to oxidative stress. In addition, DNA damage is a partly common circumstance in cell life and may result in mutation, cancer, and even cell death. Recently, accumulating evidence illustrated that the MEK/ERK pathway is associated with the suitable performance of cellular DNA damage response (DDR), the main pathway of tumor suppression. During DDR, the MEK/ERK pathway is regularly activated, which contributes to the appropriate activation of DDR checkpoints to inhibit cell division. Therefore, the aim of this review is to comprehensively discuss the critical function of MAPK signaling in oxidative stress, DNA damage, and cancer progression. During DNA damage response, the RAS/MAPK pathway is regularly activated, which contributes to the appropriate activation of DDR checkpoints to inhibit cell division.