The p38/MKP-1 signaling axis in oral cancer: Impact of tumor-associated macrophages

Abstract

Oral squamous cell carcinomas (OSCC) constitute over 95% of all head and neck malignancies. As a key component of the tumor microenvironment (TME), chronic inflammation contributes towards the development, progression, and regional metastasis of OSCC. Tumor associated macrophages (TAMs) associated with OSSC promote tumorigenesis through the production of cytokines and pro-inflammatory factors that are critical role in the various steps of malignant transformation, including tumor growth, survival, invasion, angiogenesis, and metastasis. The mitogen-activated protein kinases (MAPKs) can regulate inflammation along with a wide range of cellular processes including cell metabolism, proliferation, motility, apoptosis, survival, differentiation and play a crucial role in cell growth and survival in physiological and pathological processes including innate and adaptive immune responses. Dual specificity MAPK phosphatases (MKPs) deactivates MAPKs. MKPs are considered as an important feedback control mechanism that limits MAPK signaling and subsequent target gene expression. This review outlines the role of MKP-1, the founding member of the MKP family, in OSCC and the TME. Herein, we summarize recent progress in understanding the regulation of p38 MAPK/MKP-1 signaling pathways via TAM-related immune responses in OSCC development, progression and treatment outcomes.

Keywords: MKP-1; Oral cancer; Tumor microenvironment; Tumor-associated macrophages; p38 mitogen activating kinases.