JNK in tumor microenvironment : present findings and challenges in clinical translation

Abstract

Simple Summary Stress-activated c-Jun N-terminal kinases (JNKs) are members of mitogen-activated protein kinases (MAPKs). Apart from having both tumor promoting and tumor suppressing roles in cancers due to its impact on apoptosis and autophagy pathways, JNK also plays complex roles in the heterogeneous tumor microenvironment (TME) and is involved in different tumorigenesis pathways. The JNK pathway influences various stressful and chronic inflammatory conditions along with different cell populations in TME. In this review, we aim to present the current knowledge of JNK-mediated processes in TME and the challenges in clinical translation. The c-Jun N-terminal kinases (JNKs) are a group of mitogen-activated protein kinases (MAPKs). JNK is mainly activated under stressful conditions or by inflammatory cytokines and has multiple downstream targets for mediating cell proliferation, differentiation, survival, apoptosis, and immune responses. JNK has been demonstrated to have both tumor promoting and tumor suppressing roles in different cancers depending on the focused pathway in each study. JNK also plays complex roles in the heterogeneous tumor microenvironment (TME). JNK is involved in different tumorigenesis pathways. TME closely relates with tumor development and consists of various stressful and chronic inflammatory conditions along with different cell populations, in which the JNK pathway may have various mediating roles. In this review, we aim to summarize the present knowledge of JNK-mediated processes in TME, including hypoxia, reactive oxygen species, inflammation, immune responses, angiogenesis, as well as the regulation of various cell populations within TME. This review also suggests future research directions for translating JNK modulation in pre-clinical findings to clinical benefits.