Functional Roles of JNK and p38 MAPK Signaling in Nasopharyngeal Carcinoma

Abstract

c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) family members integrate signals that affect proliferation, differentiation, survival, and migration in a cell context- and cell type-specific way. JNK and p38 MAPK activities are found upregulated in nasopharyngeal carcinoma (NPC). Studies have shown that activation of JNK and p38 MAPK signaling can promote NPC oncogenesis by mechanisms within the cancer cells and interactions with the tumor microenvironment. They regulate multiple transcription activities and contribute to tumor-promoting processes, ranging from cell proliferation to apoptosis, inflammation, metastasis, and angiogenesis. Current literature suggests that JNK and p38 MAPK activation may exert pro-tumorigenic functions in NPC, though the underlying mechanisms are not well documented and have yet to be fully explored. Here, we aim to provide a narrative review of JNK and p38 MAPK pathways in human cancers with a primary focus on NPC. We also discuss the potential therapeutic agents that could be used to target JNK and p38 MAPK signaling in NPC, along with perspectives for future works. We aim to inspire future studies further delineating JNK and p38 MAPK signaling in NPC oncogenesis which might offer important insights for better strategies in diagnosis, prognosis, and treatment decision-making in NPC patients.

Investigation of the apoptosis‐inducing effect of docetaxel by comprehensive LC–MS–based metabolomics and network pharmacology approaches

“…ERKs are mainly related to cell proliferation and differentiation (Pashirzad et al, 2021; Sugiura et al, 2021). JNKs, by activating the intrinsic pathway, enables Bcl‐2 to participate in the release of pro‐apoptotic molecules, which leads to activation of caspases and ultimately cell apoptosis (Pua et al, 2022). P38MAPKs could regulate cell apoptosis by enhancing the expression of c‐Myc, phosphorylating p53, activating c‐Jun, among other functions (Pua et al, 2022).…”

“…JNKs, by activating the intrinsic pathway, enables Bcl‐2 to participate in the release of pro‐apoptotic molecules, which leads to activation of caspases and ultimately cell apoptosis (Pua et al, 2022). P38MAPKs could regulate cell apoptosis by enhancing the expression of c‐Myc, phosphorylating p53, activating c‐Jun, among other functions (Pua et al, 2022). Metabolic pathways are always complicated and even a tiny little intervention can have dramatic effects.…”

“…Bcl-2 to participate in the release of pro-apoptotic molecules, which leads to activation of caspases and ultimately cell apoptosis (Pua et al, 2022). P38MAPKs could regulate cell apoptosis by enhancing the expression of c-Myc, phosphorylating p53, activating c-Jun, among other functions (Pua et al, 2022). Metabolic pathways are always complicated and even a tiny little intervention can have dramatic effects.…”

Pan-Cancer Analysis Reveals SH3TC2 as an Oncogene for Colorectal Cancer and Promotes Tumorigenesis via the MAPK Pathway

“…MAPK inhibitors for CRC treatment have also been introduced as clinical treatments [ 56 , 57 ]. However, emerging evidence has also shown a tumor suppressor role of JNK proteins [ 20 , 54 , 58 ]. The reason for the dual role of JNK or MAPK proteins may be different crossroads in the molecular pathways.…”

ING4 Promotes Stemness Enrichment of Human Renal Cell Carcinoma Cells Through Inhibiting DUSP4 Expression to Activate the p38 MAPK/type I IFN-Stimulated Gene Signaling Pathway

“…Indeed, the functions of p38 MAPK in cancer have been widely investigated. Evidences have indicated that the stage of tumor development can strongly govern the function of p38 MAPK, with a low p38 MAPK activity generally favoring malignancy at early stages and p38 MAPK being highly activated at the advanced stages of tumorigenesis, involving migration to adjacent organs ( Martinez-Limon et al, 2020 ; Pua et al, 2022 ). In addition, the role of p38 MAPK in CSC regulation has been validated.…”