论文部分内容阅读
Histones are a family of basic proteins that associate with DNA in the nucleus and play key roles in regulating chromatin structure and dynamics.Emerging evidence indicates that histones can function as potent proinflammatory mediators of death in sepsis,but the role of extracellular histones in cell migration and invasion remains unexplored.Here,we provide evidence to support a novel role for extracellular histone in the regulation of tumor cell migration.Exogenous,dose-dependent histone protein induces hepatocellular carcinoma cell (e.g.,Huh7 and Hepa1-6) migration through Tolllike receptor (TLR)-4,but not TLR-2 and the receptor for advanced glycation endproduct.(RAGE).In addition,histone induces TLR4-mediated NF-κB activation via an ERK-dependent mechanism,which controls the expression of an array of chemokine genes (e.g.,CXCL10 and CCL9/10).Genetic or pharmacological inhibition of the TLR4-ERK-NF-kB pathway uniformly decreases histone-mediated cell migration.Collectively,these findings shed light on a novel mechanism for tumor cell migration and highlight the importance of targeting histone in the treatment of hepatocellular carcinoma.