The functions and regulatory pathways of S100A8/A9 and its receptors in cancers

Huimin Zhou; Cong Zhao; Rongguang Shao; Yanni Xu; Wuli Zhao

doi:10.3389/fphar.2023.1187741

The functions and regulatory pathways of S100A8/A9 and its receptors in cancers

Front Pharmacol. 2023 Aug 28:14:1187741. doi: 10.3389/fphar.2023.1187741. eCollection 2023.

Authors

Huimin Zhou¹, Cong Zhao¹, Rongguang Shao¹, Yanni Xu², Wuli Zhao¹

Affiliations

¹ 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.
² 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.

Abstract

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.

Keywords: RAGEs; S100A8/A9; TLR4; cancer; inflammation.

Publication types

Review

Grants and funding

This study was funded by the National Key Research and Development Program of China (2016YFA0201504), National Natural Science Foundation of China (Nos. 81473249 and 81102464), National Megaproject for Innovative Drugs (2014ZX09201042), CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-030), and Drug Innovation Major Project of China (2018ZX09711001-007-002).