文章：

原发性渗出性淋巴瘤细胞中HSP110的抑制：单一分子，多重促生存靶点

HSP110 Inhibition in Primary Effusion Lymphoma Cells: One Molecule, Many Pro-Survival Targets

原文发布日期：29 November 2023

DOI: 10.3390/cancers15235651

类型: Article

开放获取: 是

英文摘要：

Heat shock proteins (HSPs) are highly expressed in cancer cells and represent a promising target in anti-cancer therapy. In this study, we investigated for the first time the expression of high-molecular-weight HSP110, belonging to the HSP70 family of proteins, in Primary Effusion Lymphoma (PEL) and explored its role in their survival. This is a rare lymphoma associated with KSHV, for which an effective therapy remains to be discovered. The results obtained from this study suggest that targeting HSP110 could be a very promising strategy against PEL, as its silencing induced lysosomal membrane permeabilization, the cleavage of BID, caspase 8 activation, downregulated c-Myc, and strongly impaired the HR and NHEJ DNA repair pathways, leading to apoptotic cell death. Since chemical inhibitors of this HSP are not commercially available yet, this study encourages a more intense search in this direction in order to discover a new potential treatment that is effective against this and likely other B cell lymphomas that are known to overexpress HSP110.

摘要翻译： 

热休克蛋白在癌细胞中高表达，是抗癌治疗中极具前景的靶点。本研究首次探讨了属于HSP70家族的高分子量蛋白HSP110在原发性渗出性淋巴瘤中的表达情况及其对细胞存活的影响。该罕见淋巴瘤与卡波西肉瘤相关疱疹病毒密切相关，目前尚未发现有效疗法。研究结果表明靶向HSP110可能是对抗原发性渗出性淋巴瘤的潜在策略——其基因沉默可诱导溶酶体膜透化、BID蛋白裂解、caspase 8激活，下调c-Myc表达，并显著抑制同源重组与非同源末端连接DNA修复通路，最终引发细胞凋亡。鉴于目前尚无该热休克蛋白的化学抑制剂上市，本研究将推动该领域的深入研究，以期开发出针对此类及其他已知过表达HSP110的B细胞淋巴瘤的新型有效疗法。

原文链接：

HSP110 Inhibition in Primary Effusion Lymphoma Cells: One Molecule, Many Pro-Survival Targets