He Si-Jia, Cheng Jin, Feng Xiao, Yu Yang, Tian Ling, Huang Qian
Cancer Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Oncotarget. 2017 May 16;8(38):64534-64550. doi: 10.18632/oncotarget.17885. eCollection 2017 Sep 8.
High-mobility group box 1 (HMGB1) is an abundant protein in most eukaryocytes. It can bind to several receptors such as advanced glycation end products (RAGE) and Toll-like receptors (TLRs), in direct or indirect way. The biological effects of HMGB1 depend on its expression and subcellular location. Inside the nucleus, HMGB1 is engaged in many DNA events such as DNA repair, transcription, telomere maintenance, and genome stability. While outside the nucleus, it possesses more complicated functions, including regulating cell proliferation, autophagy, inflammation and immunity. During tumor development, HMGB1 has been characterized as both a pro- and anti-tumoral protein by either promoting or suppressing tumor growth, proliferation, angiogenesis, invasion and metastasis. However, the current knowledge concerning the positive and negative effects of HMGB1 on tumor development is not explicit. Here, we evaluate the role of HMGB1 in tumor development and attempt to reconcile the dual effects of HMGB1 in carcinogenesis. Furthermore, we would like to present current strategies targeting against HMGB1, its receptor or release, which have shown potentially therapeutic value in cancer intervention.
高迁移率族蛋白B1（HMGB1）是大多数真核细胞中一种丰富的蛋白质。它可以直接或间接地与多种受体结合，如晚期糖基化终产物受体（RAGE）和Toll样受体（TLRs）。HMGB1的生物学效应取决于其表达和亚细胞定位。在细胞核内，HMGB1参与许多DNA相关事件，如DNA修复、转录、端粒维持和基因组稳定性。而在细胞核外，它具有更复杂的功能，包括调节细胞增殖、自噬、炎症和免疫。在肿瘤发生发展过程中，HMGB1既被认为是一种促肿瘤蛋白，通过促进肿瘤生长、增殖、血管生成、侵袭和转移来发挥作用；又被认为是一种抗肿瘤蛋白。然而，目前关于HMGB1对肿瘤发生发展的正负效应的认识并不明确。在此，我们评估HMGB1在肿瘤发生发展中的作用，并试图调和HMGB1在致癌过程中的双重作用。此外，我们还将介绍目前针对HMGB1及其受体或释放的策略，这些策略在癌症干预中已显示出潜在的治疗价值。
