皮质极性轴控制了乳腺腺腺体结构中的休息膜潜力和Cl-共运输
Albert K Urazaev1,2, Lei Wang3, Yunfeng Bai3,4
1Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
Journal of cell science
|October 11, 2023
概括
这项研究揭示了在分化过程中表皮细胞膜潜力 (MP) 如何受到调节. 乳腺癌细胞的顶极性损失降低了MP,破坏了细胞平衡.
科学领域:
- 细胞生物学 细胞生物学
- 皮质生物学 皮质生物学
- 癌症生物学 癌症生物学
背景情况:
- 膜潜能 (MP) 对于细胞平衡至关重要,它调节分子运输和基因表达.
- 在上皮分化过程中MP的建立及其与组织架构的关系仍然不清楚.
- 了解MP调节对于理解上皮质平衡和癌症等疾病状态至关重要.
研究的目的:
- 在3D乳腺癌进展模型中,研究巴索索皮极性和静止MP之间的关系.
- 阐明在上皮分化过程中控制MP的分子机制.
- 确定MP的变化如何导致癌症的发展.
主要方法:
- 利用微电极技术在3D细胞培养中测量MP和输入电阻.
- 检查了间隙结细胞间通信 (GJIC) 和Na+/K+/2Cl-共传输体 (NKCC) 在MP调节中的作用.
- 评估了对已知NKCC抑制剂furosemide的反应中的MP变化.
主要成果:
- 静止MP由GJIC升高,促进顶极性,并由NKCC活动降低,与基底极性相关.
- 乳腺癌细胞表现出减少的GJIC和NKCC活性,与较低的MP相关.
- 诱导癌细胞的分化恢复了GJIC和NKCC的功能,但导致了最低的MP,与缺席的顶端极性有关.
结论:
- 在表皮分化和极性建立过程中,GJIC和NKCC活动是MP的关键调节者.
- 乳腺上皮质的顶极性损失会破坏细胞平衡,部分是通过减少MP.
- 癌细胞中MP和极性的失调凸显了潜在的治疗点.
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