素代谢是乳腺癌中一种新的代谢瘤抑制途径
Jianchun Wu1, Kaitrin Kramer1, David L Crowe2
1University of Illinois Cancer Center, 801 S. Paulina Street, Room 525, Chicago, IL, 60612, USA.
Oncogene
|July 1, 2023
概括
肥胖通过改变核受体功能驱动乳腺癌. 失去过氧酶增殖器激活受体γ (PPARγ) 激活了素代谢,揭示了一种新的瘤抑制途径.
科学领域:
- 在瘤学瘤学.
- 代谢途径 代谢途径
- 分子生物学分子生物学
背景情况:
- 肥胖是乳腺癌的主要可预防的原因.
- 核受体氧体增殖器激活受体γ (PPARγ) 与肥胖有关,在乳腺癌中降低.
- 肥胖微环境对乳腺癌中的核受体的影响需要进一步研究.
研究的目的:
- 开发一种模型,阐明肥胖引起的微环境变化如何影响乳腺癌中的核受体功能.
- 研究PPARγ在与肥胖相关的乳腺癌表型中的作用.
- 为了确定参与抑制乳腺癌的新代谢途径.
主要方法:
- 创建了一个新的小鼠模型来研究肥胖对乳腺癌的影响.
- 在乳腺上皮质中利用了PPARγ的遗传删除.
- 分析了基因表达,细胞增殖,自和衰老标志物.
- 研究了2-氨基酸半合酶 (AASS) 的作用及其通过PPARγ的调节.
- 研究了AASS过度表达,乙乙酸盐和HDAC抑制在人类乳腺癌细胞系和体内细胞系中的影响.
主要成果:
- 在瘦小鼠中,PPARγ 缺失意外增加了瘤潜伏期,减少了光原细胞,增强了自和衰老.
- 肥胖小鼠中PPARγ的损失调节了AASS,这是氨酸代谢的调节者.
- 在人类乳腺癌中,AASS的表达减少;其过度表达或乙乙酸治疗抑制了增殖并诱导了自/衰老.
- 抑制HDAC促进了乳腺瘤细胞的自和衰老.
结论:
- 素代谢代表了乳腺癌中一种新的代谢瘤抑制途径.
- 在肥胖的背景下,PPARγ在调节这种途径方面发挥着关键作用.
- 向素代谢或HDACs可能为与肥胖相关的乳腺癌提供治疗策略.
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