C‐Jun N‐terminal kinase signalling pathway in response to cisplatin

• Published in: Journal of cellular and molecular medicine Vol. 20; no. 11; pp. 2013 - 2019
• Main Authors: Yan, Dong, An, GuangYu, Kuo, Macus Tien
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.11.2016; John Wiley and Sons Inc
• Subjects: Activating transcription factor 2; Animals; Apoptosis; Breast cancer; Cancer therapies; Cell death; Cell Death - drug effects; Cell differentiation; Cell proliferation; Cell survival; Chemotherapy; Cisplatin; Cisplatin - pharmacology; Cytokines; Cytotoxicity; C‐Jun N‐terminal kinase signalling pathway; Deoxyribonucleic acid; Disruption; DNA; DNA biosynthesis; DNA damage; Drug resistance; Drug Resistance, Neoplasm - drug effects; Gene Regulatory Networks - drug effects; Growth factors; Humans; JNK Mitogen-Activated Protein Kinases - metabolism; JNK protein; Kinases; Lung cancer; MAP Kinase Signaling System - drug effects; Mitochondria; p53 Protein; Phosphatase; Phosphorylation; Proteins; resistance; Review; Signal transduction; Substrate inhibition; Survival; Transcription factors; Tumor necrosis factor-TNF; Tumors; C-Jun N-terminal kinase signalling pathway; apoptosis; cisplatin; resistance
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.12908

Cisplatin (cis diamminedichloroplatinum II, cDDP) is one of the most effective cancer chemotherapeutic agents and is used in the treatment of many types of human malignancies. However, inherent tumour resistance is a major barrier to effective cisplatin therapy. So far, the mechanism of cDDP resistance has not been well defined. In general, cisplatin is considered to be a cytotoxic drug, for damaging DNA and inhibiting DNA synthesis, resulting in apoptosis via the mitochondrial death pathway or plasma membrane disruption. cDDP−induced DNA damage triggers signalling pathways that will eventually decide between cell life and death. As a member of the mitogen‐activated protein kinases family, c‐Jun N‐terminal kinase (JNK) is a signalling pathway in response to extracellular stimuli, especially drug treatment, to modify the activity of numerous proteins locating in the mitochondria or the nucleus. Recent studies suggest that JNK signalling pathway plays a major role in deciding the fate of the cell and inducing resistance to cDDP‐induced apoptosis in human tumours. c‐Jun N‐terminal kinase regulates several important cellular functions including cell proliferation, differentiation, survival and apoptosis while activating and inhibiting substrates for phosphorylation transcription factors (c‐Jun, ATF2: Activating transcription factor 2, p53 and so on), which subsequently induce pro‐apoptosis and pro‐survival factors expression. Therefore, it is suggested that JNK signal pathway is a double‐edged sword in cDDP treatment, simultaneously being a significant pro‐apoptosis factor but also being associated with increased resistance to cisplatin‐based chemotherapy. This review focuses on current knowledge concerning the role of JNK in cell response to cDDP, as well as their role in cisplatin resistance.