Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Paediatric Department, Royal London Hospital, Whitechapel Road, Whitechapel, London, E1 1BB, UK.
Cell Oncol (Dordr). 2020 Apr;43(2):177-193. doi: 10.1007/s13402-019-00477-5. Epub 2019 Nov 1.
In recent years, the high mobility group box-1 (HMGB1) protein, a damage-associated molecular pattern (DAMP) molecule, has been found to play multifunctional roles in the pathogenesis of colorectal cancer. Although much attention has been given to the diagnostic and prognostic values of HMGB1 in colorectal cancer, the exact functional roles of the protein as well as the mechanistic pathways involved have remained poorly defined. This systematic review aims to discuss what is currently known about the roles of HMGB1 in colorectal cancer development, growth and progression, and to highlight critical areas for future investigations. To achieve this, the bibliographic databases Pubmed, Scopus, Web of Science and ScienceDirect were systematically screened for articles from inception till June 2018, which address associations of HMGB1 with colorectal cancer.
HMGB1 plays multiple roles in promoting the pathogenesis of colorectal cancer, despite a few contradicting studies. HMGB1 may differentially regulate disease-related processes, depending on the redox status of the protein in colorectal cancer. Binding of HMGB1 to various protein partners may alter the impact of HMGB1 on disease progression. As HMGB1 is heavily implicated in the pathogenesis of colorectal cancer, it is crucial to further improve our understanding of the functional roles of HMGB1 not only in colorectal cancer, but ultimately in all types of cancers.
近年来,高迁移率族蛋白 B1(HMGB1)作为一种损伤相关分子模式(DAMP)分子,被发现于结直肠癌的发病机制中发挥多种功能。虽然人们已经关注到 HMGB1 在结直肠癌中的诊断和预后价值,但该蛋白的确切功能作用以及涉及的机制途径仍未得到明确界定。本系统综述旨在讨论目前已知的 HMGB1 在结直肠癌发生、生长和进展中的作用,并强调未来研究的关键领域。为实现这一目标,从建库开始至 2018 年 6 月,系统地在 Pubmed、Scopus、Web of Science 和 ScienceDirect 等文献数据库中筛选了探讨 HMGB1 与结直肠癌关联的文章。
尽管有一些相互矛盾的研究,但 HMGB1 在促进结直肠癌发病机制中发挥了多种作用。HMGB1 可能通过改变其在结直肠癌中的氧化还原状态,从而差异化地调节与疾病相关的过程。HMGB1 与各种蛋白伴侣的结合可能改变 HMGB1 对疾病进展的影响。由于 HMGB1 与结直肠癌的发病机制密切相关,因此进一步提高我们对 HMGB1 功能作用的理解至关重要,不仅要了解 HMGB1 在结直肠癌中的作用,而且最终要了解 HMGB1 在所有类型癌症中的作用。