Zhou Huimin, Zhao Cong, Shao Rongguang, Xu Yanni, Zhao Wuli
State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Antibiotic Bioengineering, Ministry of Health, Laboratory of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
NHC Key Laboratory of Biotechnology of Antibiotics, National Center for New Microbial Drug Screening, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Pharmacol. 2023 Aug 28;14:1187741. doi: 10.3389/fphar.2023.1187741. eCollection 2023.
Inflammation primarily influences the initiation, progression, and deterioration of many human diseases, and immune cells are the principal forces that modulate the balance of inflammation by generating cytokines and chemokines to maintain physiological homeostasis or accelerate disease development. S100A8/A9, a heterodimer protein mainly generated by neutrophils, triggers many signal transduction pathways to mediate microtubule constitution and pathogen defense, as well as intricate procedures of cancer growth, metastasis, drug resistance, and prognosis. Its paired receptors, such as receptor for advanced glycation ends (RAGEs) and toll-like receptor 4 (TLR4), also have roles and effects within tumor cells, mainly involved with mitogen-activated protein kinases (MAPKs), NF-κB, phosphoinositide 3-kinase (PI3K)/Akt, mammalian target of rapamycin (mTOR) and protein kinase C (PKC) activation. In the clinical setting, S100A8/A9 and its receptors can be used complementarily as efficient biomarkers for cancer diagnosis and treatment. This review comprehensively summarizes the biological functions of S100A8/A9 and its various receptors in tumor cells, in order to provide new insights and strategies targeting S100A8/A9 to promote novel diagnostic and therapeutic methods in cancers.
炎症主要影响多种人类疾病的发生、发展和恶化，免疫细胞是通过产生细胞因子和趋化因子来调节炎症平衡以维持生理稳态或加速疾病发展的主要力量。S100A8/A9是一种主要由中性粒细胞产生的异二聚体蛋白，它触发许多信号转导途径来介导微管构成和病原体防御，以及癌症生长、转移、耐药性和预后等复杂过程。其配对受体，如晚期糖基化终末产物受体（RAGEs）和Toll样受体4（TLR4），在肿瘤细胞内也具有作用和影响，主要涉及丝裂原活化蛋白激酶（MAPKs）、核因子κB（NF-κB）、磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）、雷帕霉素靶蛋白（mTOR）和蛋白激酶C（PKC）的激活。在临床环境中，S100A8/A9及其受体可作为癌症诊断和治疗的有效生物标志物互补使用。本综述全面总结了S100A8/A9及其各种受体在肿瘤细胞中的生物学功能，以便为靶向S100A8/A9促进癌症新诊断和治疗方法提供新的见解和策略。
