JNK pathway in osteosarcoma: pathogenesis and therapeutics

Abstract

Context: The c-Jun NH2-terminal kinase (JNK) is a member of the mitogen-activated protein kinase super family. JNK can phosphorylate a number of activator protein-1 components, activating several transcription factors, and thus, JNK signaling pathway is being involved in several carcinogenic mechanisms. Objective: In this study, we have reviewed the recent updates of the association of JNK pathway with osteosarcoma (OS), which is one of the most common and aggressive bone malignancies. Methods: In this review, we have explored the databases like PubMed, Google Scholar, MEDLINE, etc., and collected the most relevant papers of JNK signaling pathway involved in the pathogenesis and therapeutics of OS. Results: Evidence showed that JNK is a master protein kinase that plays an important role in osteoblast proliferation, differentiation and apoptosis. Interesting reports showed that chemical JNK inhibitors reduce OS cell proliferation and metastasis. Many of the components of this pathway have now been identified and the application of JNK inhibitors has been proven to work in vivo in human and in animal models; however, JNK pathway has not been translated into clinical use. Conclusion: Therapeutic interventions of potent and selective inhibitors of JNK might provide promising therapeutic approaches for the treatment of OS, and could improve the survival rate and quality of life of OS patients.

• c-Jun NH2-terminal kinase pathway
• JNK inhibitors
• matrix metalloproteinase
• mitogen-activated protein kinase
• osteosarcoma

Declaration of interest

This work was supported by the National Natural Science Foundation of China (No. 81402224), the Provincial Science Foundation of Hunan (No. 2015JJ3139), the Scientific Research Project of Science and Technology Bureau of Hunan Province (2012FJ6001), the Scientific Research Project of Science and Technology Office of Changsha City (K1203040-31), the Scientific Research Project of Health and Family Planning Commission of Hunan Province (B2014-12) and the College students’ Innovation and Entrepreneurship Project of Central South University (DL14505). The authors report no declarations of interest.