HMGB1/RAGE axis in tumor development: unraveling its significance

Anqi Fan; Mengxiang Gao; Xuhuan Tang; Mengya Jiao; Chenchen Wang; Yingying Wei; Quan Gong; Jixin Zhong

doi:10.3389/fonc.2024.1336191

HMGB1/RAGE axis in tumor development: unraveling its significance

Front Oncol. 2024 Mar 1:14:1336191. doi: 10.3389/fonc.2024.1336191. eCollection 2024.

Authors

Anqi Fan¹, Mengxiang Gao¹, Xuhuan Tang², Mengya Jiao², Chenchen Wang³, Yingying Wei⁴, Quan Gong⁵, Jixin Zhong⁴

Affiliations

¹ College of Life Science, Yangtze University, Jingzhou, Hubei, China.
² Department of Immunology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonostic Infectious Disease, Huazhong University of Science and Technology, Wuhan, Hubei, China.
³ National Demonstration Center for Experimental Basic Medical Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China.
⁵ Department of Immunology, School of Medicine, Yangtze University, Jingzhou, Hubei, China.

Abstract

High mobility group protein 1 (HMGB1) plays a complex role in tumor biology. When released into the extracellular space, it binds to the receptor for advanced glycation end products (RAGE) located on the cell membrane, playing an important role in tumor development by regulating a number of biological processes and signal pathways. In this review, we outline the multifaceted functions of the HMGB1/RAGE axis, which encompasses tumor cell proliferation, apoptosis, autophagy, metastasis, and angiogenesis. This axis is instrumental in tumor progression, promoting tumor cell proliferation, autophagy, metastasis, and angiogenesis while inhibiting apoptosis, through pivotal signaling pathways, including MAPK, NF-κB, PI3K/AKT, ERK, and STAT3. Notably, small molecules, such as miRNA-218, ethyl pyruvate (EP), and glycyrrhizin exhibit the ability to inhibit the HMGB1/RAGE axis, restraining tumor development. Therefore, a deeper understanding of the mechanisms of the HMGB1/RAGE axis in tumors is of great importance, and the development of inhibitors targeting this axis warrants further exploration.

Keywords: HMGB1; HMGB1/RAGE axis; RAGE; development; tumor.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China(82270893).