Tang Daolin, Kang Rui, Zeh Herbert J, Lotze Michael T
The DAMP Laboratory, Department of Surgery, G.27 Hillman Cancer Center, University of Pittsburgh Cancer Institute, 5117 Centre Ave., Pittsburgh, PA 15213, USA.
Biochim Biophys Acta. 2010 Jan-Feb;1799(1-2):131-40. doi: 10.1016/j.bbagrm.2009.11.014.
High-mobility group box 1 protein (HMGB1), a chromatin associated nuclear protein and extracellular damage associated molecular pattern molecule (DAMP), is an evolutionarily ancient and critical regulator of cell death and survival. Overexpression of HMGB1 is associated with each of the hallmarks of cancer including unlimited replicative potential, ability to develop blood vessels (angiogenesis), evasion of programmed cell death (apoptosis), self-sufficiency in growth signals, insensitivity to inhibitors of growth, inflammation, tissue invasion and metastasis. Our studies and those of our colleagues suggest that HMGB1 is central to cancer (abnormal wound healing) and many of the findings in normal wound healing as well. Here, we focus on the role of HMGB1 in cancer, the mechanisms by which it contributes to carcinogenesis, and therapeutic strategies based on targeting HMGB1.
高迁移率族蛋白B1(HMGB1)是一种与染色质相关的核蛋白,也是细胞外损伤相关分子模式分子(DAMP),是一种在进化上古老且关键的细胞死亡和存活调节因子。HMGB1的过表达与癌症的每一个特征相关,包括无限增殖潜能、血管生成能力(血管生成)、逃避程序性细胞死亡(凋亡)、生长信号的自给自足、对生长抑制剂不敏感、炎症、组织侵袭和转移。我们和同事的研究表明,HMGB1在癌症(异常伤口愈合)以及正常伤口愈合的许多发现中都起着核心作用。在这里,我们重点关注HMGB1在癌症中的作用、其促进致癌作用的机制以及基于靶向HMGB1的治疗策略。