GJB2通过细胞质转移激活糖解,并基于单细胞RNA测序生成抑制性瘤微环境,促进HCC的进展
Hanyuan Liu1,2, Xiao Li1, Chenwei Zhang1
1Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210000, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|August 20, 2024
概括
间隙结蛋白β-2 (GJB2) 通过增加糖解和创造抑制瘤环境,驱动肝细胞癌 (HCC) 的进展. 用Salvianolic acid B针对GJB2可能会改善HCC患者的抗PD1疗法的有效性.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 肝细胞癌 (HCC) 通常在晚期呈现,需要超出手术选择的新型治疗点.
- 识别HCC进展的分子驱动因素对于开发治疗晚期疾病的有效疗法至关重要.
研究的目的:
- 研究隙结蛋白β-2 (GJB2) 在肝细胞癌 (HCC) 进展中的作用.
- 探索GJB2影响HCC的分子机制,包括其对细胞局部化,代谢途径和瘤免疫微环境的影响.
- 评估向GJB2的治疗潜力,特别是与现有疗法 (如抗PD1治疗) 结合使用.
主要方法:
- 单细胞RNA测序用于识别恶性HCC细胞中的GJB2丰富.
- 对GJB2表达水平和患者预后进行了分析.
- 使用免疫组织化学或类似的技术来确定GJB2在正常与癌症肝脏组织中的定位.
- 进行了涉及GJB2淘汰的实验,以评估其对瘤微环境的影响.
- 评估了沙尔维阿诺酸B对GJB2活性和抗PD1治疗敏感性的影响.
主要成果:
- 间隙结蛋白β-2 (GJB2) 在恶性HCC细胞中高度表达,与更糟糕的预后相关.
- 与正常的肝脏组织 (细胞膜) 相比,GJB2在HCC细胞 (细胞质和核) 中表现出改变的亚细胞局部.
- 通过激活糖解,GJB2促进HCC的进展,通过IκBa无化对NF-κB通路进行上调,并激活HIF-1α/GLUT-1/PD-L1通路.
- GJB2的击倒改变了瘤的免疫微环境.
- 萨尔维阿诺酸B抑制了GJB2的活性,并增强了对抗PD1疗法的敏感性.
结论:
- GJB2是HCC进展的关键驱动因素,通过细胞质转移促进糖解和免疫抑制.
- 用Salvianolic acid B针对GJB2提供了一种有希望的策略,以提高HCC中抗PD1疗法的疗效.
- 这些发现为开发用于肝细胞癌的新型组合治疗策略提供了基础.
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