JNK signaling in cancer cell survival

Abstract

c‐Jun N‐terminal kinase (JNK) is involved in cancer cell apoptosis; however, emerging evidence indicates that this Janus signaling promotes cancer cell survival. JNK acts synergistically with NF‐κB, JAK/STAT, and other signaling molecules to exert a survival function. JNK positively regulates autophagy to counteract apoptosis, and its effect on autophagy is related to the development of chemotherapeutic resistance. The prosurvival effect of JNK may involve an immune evasion mechanism mediated by transforming growth factor‐β, toll‐like receptors, interferon‐γ, and autophagy, as well as compensatory JNK‐dependent cell proliferation. The present review focuses on recent advances in understanding the prosurvival function of JNK and its role in tumor development and chemoresistance, including a comprehensive analysis of the molecular mechanisms underlying JNK‐mediated cancer cell survival. There is a focus on the specific “Yin and Yang” functions of JNK1 and JNK2 in the regulation of cancer cell survival. We highlight recent advances in our knowledge of the roles of JNK in cancer cell survival, which may provide insight into the distinct functions of JNK in cancer and its potential for cancer therapy.

A risk signature with four autophagy‐related genes for predicting survival of glioblastoma multiforme

“…Consistent with our results, another research shows that GBM patients with higher expression level of LGALS8 have poorer prognosis . Mitogen‐activated protein kinase 8 (MAPK8), also known as JNK1, belongs to JNK kinase family that consists of three members: JNK1, JNK2 and JNK3 . JNK directly binds and promotes phosphorylation of several transcription factors, such as NFAT, c‐Jun and JunB, and regulates multiple biological processes, including immune cell differentiation, inflammation, cancer progression and especially programmed cell death .…”

“…Mitogen‐activated protein kinase 8 (MAPK8), also known as JNK1, belongs to JNK kinase family that consists of three members: JNK1, JNK2 and JNK3 . JNK directly binds and promotes phosphorylation of several transcription factors, such as NFAT, c‐Jun and JunB, and regulates multiple biological processes, including immune cell differentiation, inflammation, cancer progression and especially programmed cell death . JNK can trigger apoptosis, promote necroptosis, involve in non‐canonical pyroptotic signalling and induce autophagy by different molecular mechanisms .…”

Two-Faced: Roles of JNK Signalling During Tumourigenesis in the Drosophila Model

“…Finally, it is worth reiterating the relevance of Drosophila studies to explorations of mammalian genetics and disease. We have touched upon how JNK signalling has two faces in humans, as it does in flies -it can be both pro-and anti-tumourigenic (or pro-and anti-survival), depending on the context (reviewed in Wagner and Nebreda, 2009;Wu et al, 2019). The inherently increased complexity of human JNK signalling makes the pathway difficult to work with, however, and this leaves Drosophila research at an advantage, able to use parallels between the highly conserved systems to position itself as a foundational body of knowledge for the field -conclusions drawn in flies can be adapted and extended into mammalian research.…”

“…With such diverse functionality, it is perhaps no surprise that JNK signalling has also emerged as a key player in tumourigenesis in Drosophila, something it shares with its mammalian orthologue (reviewed in Wagner and Nebreda, 2009;Wu et al, 2019). Almost all human orthologues of the core JNK signalling hierarchy have been implicated in multiple cancers, though their roles are often not well understood, and are often context dependent.…”

Melatonin mediates mucosal immune cells, microbial metabolism, and rhythm crosstalk: A therapeutic target to reduce intestinal inflammation

“…The activation of MT1/MT2 receptors by melatonin also triggers other signaling pathways, including nuclear factor κ‐light‐chain‐enhancer of activated B cells (NF‐κB), mitogen‐activated protein kinases (MAPK), extracellular‐signal‐regulated kinases 1/2 (ERK1/2), phospholipase C/protein kinase (PLC/PKC), etc. (Figure ) These pathways are involved in multiple regulatory processes from chronobiological regulation to cellular responses to various injuries such as apoptosis …”