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.
Highlights
Nasopharyngeal carcinoma (NPC) is one of the most aggressive types of head and neck carcinoma that mainly grows at the epithelial lining of the nasopharynx, with frequent metastasis to regional lymph nodes and occasionally to distal organs [1,2,3]
This review summarizes the potential therapeutics that could be used to target Jun N-terminal kinase (JNK) and p38 Mitogen-activated protein kinase (MAPK) signaling in NPC, along with perspectives for future works to address the research gaps
JNK1/2 was inactivated in human lung squamous cell carcinoma (LSCC) and their activities were positively correlated with survival rates of patients. p-JNK was overexpressed in papillary thyroid carcinomas and was significantly associated with the presence of lymph node metastases and advanced TNM stages
Summary
Nasopharyngeal carcinoma (NPC) is one of the most aggressive types of head and neck carcinoma that mainly grows at the epithelial lining of the nasopharynx, with frequent metastasis to regional lymph nodes and occasionally to distal organs [1,2,3]. Mitogen-activated protein kinase (MAPK) pathway is an intracellular signal transduction pathway that regulates a plethora of cellular processes, including cell growth, cell proliferation, cell differentiation, stress response, migration, and apoptosis, in response to various extracellular stimuli [12,13,14]. It consists of three pathways which involve extracellular-signal-regulated kinase 1 and 2 (ERK1/2), c-Jun N-terminal kinase 1, 2, and 3 (JNK1/2/3), and p38 MAPK signaling pathways (Figure 1) [15]. The activated MAPKs translocate to the nucleus and trigger cellular responses
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have