细胞外蛋白作为营养物的利用被mTORC1抑制
Wilhelm Palm1, Youngkyu Park2, Kevin Wright2
1Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Cell
|July 7, 2015
概括
哺乳动物细胞可以使用巨型皮诺细胞酶来从细胞外蛋白质中获得必需的氨基酸. 抑制mTORC1通过促进细胞依赖这种营养源时蛋白质分解来增强细胞增殖.
科学领域:
- 细胞生物学 细胞生物学
- 代谢途径 代谢途径
- 癌症研究 癌症研究
背景情况:
- 哺乳动物细胞优先代谢葡萄糖和氨基酸.
- 细胞外蛋白质的Ras诱导的巨型皮诺细胞形成可以降低转化细胞中的谷氨酸依赖性.
研究的目的:
- 为了调查蛋白质巨细胞酶是否可以作为必需氨基酸的来源.
- 了解mTORC1激活在利用细胞外蛋白供氨基酸供应的细胞中的作用.
- 探索调节mTORC1在癌症中的治疗潜力.
主要方法:
- 利用巨型皮诺细胞酶来内化细胞外蛋白质.
- 评估了蛋白质的溶酶体降解.
- 测量了mTORC1激活和细胞增殖.
- 在体外和体外模型 (瘤) 中抑制mTORC1活性.
主要成果:
- 蛋白质巨细胞形成为细胞生存提供必需的氨基酸.
- 通过细胞外蛋白激活mTORC1,维持生存,但抑制增殖.
- 抑制mTORC1增强了内细胞化蛋白质的催化作用.
- 抑制mTORC1在营养缺乏的条件和瘤中促进细胞增殖.
结论:
- 通过防止蛋白质消耗,mTORC1激活将细胞生长与自由氨基酸的可用性相结合.
- 调节mTORC1活动为癌症提供了潜在的治疗策略,特别是在营养缺乏的瘤微环境中.
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