Cancer Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
Shanghai Key Laboratory for Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
Cell Death Dis. 2018 May 29;9(6):648. doi: 10.1038/s41419-018-0626-6.
Tumor repopulation during therapy is an important cause of treatment failure. Strategies to overcome repopulation are arising in parallel with advances in the comprehension of underlying biological mechanisms. Here, we reveal a new mechanism by which high mobility group box 1 (HMGB1) released by dying cells during radiotherapy or chemotherapy could stimulate living tumor cell proliferationInhibition or genetic ablation of HMGB1 suppressed tumor cell proliferation. This effect was due to binding of HMGB1with the member receptor for advanced glycation end-products (RAGE), which activated downstream ERK and p38 signaling pathway and promoted cell proliferation. Furthermore, higher HMGB1 expression in tumor tissue correlated with poor overall survival and higher HMGB1 concentration was detected in serum of patients who accepted radiotherapy. Collectively, the results from this study suggested that interaction between dead cells and surviving cells might influence the fate of tumor. HMGB1 could be a novel tumor promoter with therapeutic and prognostic relevance in cancers.
治疗过程中的肿瘤再增殖是治疗失败的一个重要原因。随着对潜在生物学机制理解的深入，克服再增殖的策略也在不断涌现。在这里，我们揭示了一个新的机制，即在放射治疗或化学治疗过程中死亡细胞释放的高迁移率族蛋白 B1（HMGB1）可以刺激存活的肿瘤细胞增殖。抑制或基因敲除 HMGB1 可抑制肿瘤细胞增殖。这种作用是由于 HMGB1 与晚期糖基化终产物（RAGE）的成员受体结合，激活下游 ERK 和 p38 信号通路，促进细胞增殖。此外，肿瘤组织中 HMGB1 的高表达与总生存率降低相关，并且在接受放射治疗的患者的血清中检测到更高的 HMGB1 浓度。总的来说，这项研究的结果表明，死亡细胞与存活细胞之间的相互作用可能会影响肿瘤的命运。HMGB1 可能是一种具有治疗和预后相关性的新型肿瘤促进剂，与癌症有关。
