在乳腺瘤中通过SPCA2对Orai1的独立于储存的激活
Mingye Feng1, Desma M Grice, Helen M Faddy
1Department of Physiology, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA.
Cell
|October 5, 2010
概括
分泌途径Ca2+) -ATPase 2 (SPCA2) 的上调促进乳腺癌,通过增加通过Orai1. 抑制SPCA2降低了水平和瘤生长,揭示了一个新的瘤发生途径.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 离子 (Ca2+) 是重要的第二信使,调节细胞过程.
- 改变的细胞质Ca2+动态与瘤发生有关,影响了运动性,增殖和亡.
研究的目的:
- 调查分泌途径Ca2+-ATPase 2 (SPCA2) 在乳腺癌中的作用.
- 阐明SPCA2影响信号传导和瘤发生性的机制.
主要方法:
- 在乳腺癌细胞和瘤中SPCA2表达的分析.
- 功能性测试,以评估SPCA2抑制对Ca2+水平和瘤发生性的影响.
- 调查SPCA2与商店运营的Ca2+通道Orai1.1.之间的相互作用.
主要成果:
- 在乳腺癌细胞和瘤中,SPCA2被上调.
- 抑制SPCA2会降低基础Ca2+水平,并减弱瘤性.
- 通过Orai1,SPCA2增强了Ca2+的流入,独立于ER Ca2+储存和STIM蛋白.
- 与Orai1结合的SPCA2的N端激活了Ca2+的流入.
结论:
- SPCA2-Orai1复合体形成了一种促进瘤发生的新信号通路.
- 这一途径涉及构成性,独立于存储的Ca2+信号传输.
- 针对SPCA2-Orai1相互作用可能为乳腺癌提供治疗策略.
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