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溶解体囊中的氨酸储存增强了癌细胞对氧化应激的耐受性

Lixin He¹, Jinxin Chen¹, Pinwei Deng¹

¹Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

|September 26, 2023

概括

乳腺癌细胞在溶酶体中储存cyst(e) 氨酸,使用MFSD12进行谷氨合成,防止氧化应激. 抑制MFSD12可能为癌症治疗提供新的治疗策略.

科学领域:

细胞生物学细胞生物学
生物化学生物化学
在瘤学瘤学.

背景情况:

谷氨酸 (GSH) 通过防止氧化应激,对癌细胞存活至关重要.
lysosomal 囊中的e) 氨酸储存与细胞的氧化还原调节有关,但其精确的机制尚未完全理解.

研究的目的:

阐明 lysosomal 囊在癌细胞氧化还原恒温中所起的作用.
确定参与溶酶体囊中蛋白质运输及其调节的关键蛋白质.

主要方法:

研究了含有12 (MFSD12) 和囊素 (CTNS) 的主要促进者超级家族域在溶酶体囊中存储的功能.
利用乳腺癌的细胞培养模型和生物化学分析来评估谷氨水平和氧化应激.
研究了mTORC1信号在MFSD12功能和溶酶体酸化中的调节作用.

主要成果:

乳腺癌细胞对MFSD12进行上调,以增强溶酶体囊中的氨基酸储存,支持谷氨合成.
通过CTNS释放MFSD12介导的囊缓冲氧化应激并促进细胞适应.
在T254处,mTORC1直接酸化MFSD12,在应激反应中调节 lysosomal cyst{}e) 胺水平.
一个MFSD12-T254A突变导致溶酶体囊的储存受损并抑制了瘤的进展.
在乳腺癌患者中,MFSD12过度表达与新辅助化疗反应不佳和不良预后相关.

结论:

由MFSD12和CTNS调节的溶酶体囊e) 氨酸储存对于癌细胞的适应性氧化还原稳定至关重要.
MFSD12代表了改善癌症治疗结果的潜在治疗标.

关键词:

这就是为什么CTNS是CTNS.这是GSHGSH.MFSD12 金融服务中心乳腺癌乳腺癌乳腺癌化学疗法化疗化疗囊 (Cyst) 是一种 lysosome 溶解酶体是如何形成的在 mTORC1 的情况下,mTORC1 是氧化应激是一种氧化应激.氧化还原稳态 (redox homeostasis) 是一种反氧化稳态.

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