而SRP19和蛋白质分泌机制是癌症中的一个可向的弱点,与APC损失有关
Xinqi Xi1, Ling Liu1, Natasha Tuano2
1Department of Biochemistry and Molecular Biology and Cancer Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
概括
形多样性肠杆菌 (APC) 瘤抑制基因的丢失在结直肠癌中造成了脆弱性. 用低剂量的三氧化来准SRP19,通过诱导ER压力来抑制癌细胞的增殖.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症遗传学 癌症遗传学
背景情况:
- 腺多发性胆固醇 (APC) 瘤抑制基因的丧失是结直肠癌发展的关键事件.
- 目前,直接准瘤抑制基因是不可能的,这使得患有APC缺乏瘤的患者没有治疗选择.
研究的目的:
- 为了确定结直肠癌与异合体APC损失的独特脆弱性.
- 探索针对这种脆弱性的治疗策略.
主要方法:
- 研究了位于APC附近的SRP19在APC损失的癌症中的作用.
- 评估了异构细胞APC/SRP19损失对SRP19水平和蛋白质分泌的影响.
- 研究了低剂量三氧化对SRP19缺乏细胞和动物模型的影响.
主要成果:
- 异合体损失APC和SRP19导致SRP19的表达减少.
- SRP19是信号识别粒子形成的速度限制,影响蛋白质分泌和增加ER压力.
- 低剂量的三氧化有效地抑制了细胞系和动物模型中APC/SRP19损失的增殖.
结论:
- 确定了SRP19和蛋白质分泌途径是缺少APC的大肠直肠癌的脆弱性.
- 证明低剂量三氧化可以成为这些癌症的治疗策略.
- 为识别和翻译与瘤抑制基因丢失相关的漏洞提供了一个框架.
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