功能基因组学揭示,血清素合成途径在乳腺癌中至关重要
Richard Possemato1, Kevin M Marks, Yoav D Shaul
1Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA.
研究人员确定了糖酸脱酶 (PHGDH) 作为侵袭性乳腺癌的关键代谢标. 抑制PHGDH通过破坏血清素合成途径和活体中谷氨胺代谢来阻止瘤生长.
科学领域:
- 在瘤学瘤学.
- 代谢途径 代谢途径
- 基因功能 基因功能
背景情况:
- 癌细胞重编程新陈代谢以促进生长和扩散.
- RNA干扰 (RNAi) 查是识别癌症标的强大工具.
- 在体内查模型对于理解瘤发生至关重要.
研究的目的:
- 开发和应用一种负选择RNAi查方法,用于识别新型癌症标.
- 为了确定体内乳腺癌生长所必需的代谢基因.
- 研究糖酸脱酶 (PHGDH) 在乳腺癌中的作用.
主要方法:
- 使用人类乳腺癌异种移植模型开发了一种体内负选择RNAi选方法.
- 选了与侵袭性乳腺癌和干性相关的代谢基因.
- 利用RNA干扰来抑制乳腺癌细胞系中的PHGDH表达.
主要成果:
- 确定了糖酸脱酶 (PHGDH) 作为体内瘤发生的关键基因.
- 在ER阴性乳腺癌中,PHGDH过度表达,并驱动血清蛋白生物合成.
- 抑制PHGDH降低了细胞增殖和血清蛋白合成,影响TCA循环.
- 抑制PHGDH降低了alpha-ketoglutarate水平,这是TCA循环的中间体.
结论:
- 某些乳腺癌的生长取决于PHGDH驱动的血清蛋白合成途径的流动.
- PHGDH是攻击性乳腺癌的潜在治疗点.
- 在体内负选择RNAi选对于发现抗癌点是有效的.
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