丝裂原激活蛋白激酶 (MAPK) 是丝氨酸/苏氨酸蛋白激酶，在将细胞外信号传递到细胞内环境方面发挥着至关重要的作用，影响广泛的细胞过程，包括增殖、分化、凋亡、代谢活动、免疫功能和应激反应。 MAPK4 是一种非经典 MAPK，在多种恶性肿瘤中经常过度表达，包括前列腺癌、乳腺癌、宫颈癌、甲状腺癌和神经胶质瘤。它通过 AKT/mTOR 和/或 PDK1 信号通路协调细胞增殖、迁移和凋亡，从而促进肿瘤细胞生长。此外，MAPK4的表达与PI3K和PARP1等特异性抑制剂的有效性密切相关，也与癌症患者的生存率相关。越来越多的证据强调 MAPK4 参与肿瘤微环境、调节免疫反应和炎症相关疾病。本综述全面探讨了 MAPK4 的结构、功能和致癌作用，加深了对其在肿瘤发生中的激活和作用机制的了解，这可能有助于开发癌症管理的创新治疗策略。版权所有 © 2024。出版者爱思唯尔有限公司

Mitogen-Activated Protein Kinases (MAPKs) are serine/threonine protein kinases that play a crucial role in transmitting extracellular signals to the intracellular environment, influencing a wide range of cellular processes including proliferation, differentiation, apoptosis, metabolic activities, immune function and stress response. MAPK4, a non-classical MAPK, is frequently overexpressed in various malignancies, including prostate, breast, cervix, thyroid, and gliomas. It orchestrates cell proliferation, migration, and apoptosis via the AKT/mTOR and/or PDK1 signaling pathways, thus facilitating tumor cell growth. Furthermore, MAPK4 expression is closely associated with the effectiveness of specific inhibitors like PI3K and PARP1, and also correlate with the survival rates of cancer patients. Increasing evidence highlights MAPK4's involvement in the tumor microenvironment, modulating immune response and inflammation-related diseases. This review comprehensively explores the structure, function, and oncogenic role of MAPK4, providing a deeper understanding of its activation and mechanisms of action in tumorigenesis, which might be helpful for the development of innovative therapeutic strategies for cancer management.Copyright © 2024. Published by Elsevier B.V.