血清限制改变了脂多样性以限制瘤生长
Thangaselvam Muthusamy1, Thekla Cordes1, Michal K Handzlik1
1Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Nature
|August 14, 2020
概括
限制血清和甘氨酸的可用性会诱导毒性脱氧脂的合成,减缓瘤的生长. 向血清棕转移酶 (SPT) 或糖酸脱酶 (PHGDH) 提供了新的癌症治疗策略.
科学领域:
- 生物化学
- 代谢途径
- 癌症生物学
背景情况:
- 非必需的氨基酸如血清和甘氨酸对于瘤的进展至关重要.
- 对脂质代谢的分子机制和影响尚未完全理解.
- 血清棕转移酶 (SPT) 合成脂和脱氧脂.
研究的目的:
- 研究氨基酸代谢如何影响脱氧脂合成和瘤进展.
- 探索针对性SPT和癌症治疗的相关途径.
主要方法:
- 通过利用SPT变性来调节内源性脱氧脂合成.
- 分析涉及酸盐,酸盐和酸盐的代谢网络.
- 在老鼠异种移植模型中使用饮食限制 (氨酸/甘氨酸) 和药物抑制剂 (SPT,PHGDH).
主要成果:
- 固独立生长重新编程了新陈代谢网络,导致脱氧脂的积累.
- 向线粒体的pyruvate载体减轻了脱氧脂的合成,并改善了球状体的生长.
- 通过饮食限制血清蛋白/ 葡萄糖蛋白和抑制PHGDH,通过诱导脱氧脂减少了瘤的生长.
结论:
- SPT的杂乱性将氨酸和氨酸代谢与脂质多样性联系在一起,使瘤对代谢压力敏感.
- 通过氨基酸代谢调节脱氧脂合成是一种可行的抗癌策略.
- 针对SPT或PHGDH为癌症治疗提供了潜在的治疗途径.
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