在癌症中,自解体外细胞分裂将Src酶逆转到癌症细胞表面
Corleone S Delaveris1, Rita P Loudermilk2, Apurva Pandey3
1Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.
概括
原始瘤基因Src通过自酶体外细胞化 (ALE) 在癌细胞表面被发现. 瘤中的这种细胞外Src (eSrc) 可以通过抗体疗法向癌症治疗.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 在各种癌症中经常观察到Src原瘤基因的过度表达.
- 在癌细胞中Src的精确定位和运输机制仍然不完全理解.
研究的目的:
- 研究癌症中Src的非正规转位和细胞表面定位.
- 确定负责细胞外Src (eSrc) 运输的分泌途径.
- 评估针对eSrc的治疗潜力.
主要方法:
- 在体外和体内癌症模型.
- 在癌症细胞系中对自酶体外细胞 (ALE) 的分析.
- 在初级瘤中检测细胞外膜相关的Src (eSrc).
- 在细胞培养和老鼠异种移植模型中评估基于抗Src抗体的治疗方法.
主要成果:
- 在癌症中,Src被非正规地转位并倒置到细胞表面.
- 自解体外细胞分裂 (ALE) 是一种关键的分泌机制,用于将Src和其他膜固的蛋白质运输到细胞外部.
- 细胞外膜相关的Src (eSrc) 存在于人类初级瘤中.
- 抗Src抗体疗法在体外杀死瘤细胞和体内减少瘤生长方面表现出有效性.
结论:
- 细胞内蛋白质,如N-myristoylated Src,可以在拓上倒置,并在癌细胞表面呈现.
- 这种细胞外Src (eSrc) 代表了基于抗体的癌症治疗的脆弱目标.
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