细胞极性蛋白质在应对代谢压力的过程中促进了巨型皮诺细胞形成
bioRxiv : the preprint server for biology
|January 31, 2024
概括
癌细胞使用巨型皮诺细胞形成来吸收营养. 非典型蛋白激酶Cs (aPKCs) 调节胰腺癌中的这一过程,有助于在营养压力下生存.
科学领域:
- 细胞生物学 细胞生物学
- 癌症新陈代谢 癌症新陈代谢
- 分子瘤学分子瘤学
背景情况:
- 巨细胞瘤是癌细胞利用的营养清除途径,以在营养缺乏的瘤微环境中生存.
- 胰腺管道腺癌 (PDAC) 细胞严重依赖谷氨酸; 缺乏谷氨酸会增强巨型皮诺细胞体,通过氨基酸生产逃离代谢应激.
研究的目的:
- 为了确定胰腺癌细胞中巨细胞细胞形成的新型调节剂.
- 阐明细胞极性蛋白在谷氨酸压力诱导的巨皮诺细胞形成中的作用.
- 了解aPKCs,细胞极性和PDAC中的巨细胞细胞形成之间的机制联系.
主要方法:
- 研究了aPKCs (PKCζ和PKCι) 在调节巨细胞细胞的作用.
- 评估了在PDAC巨型皮诺细胞瘤中对细胞极性蛋白 (Par3,Par6) 的要求.
- 通过EGFR信号和CREM检查了aPKCs的调节.
- 研究了Par3转移到微管中的dynein依赖机制.
- 评估了aPKC枯竭和巨细胞修复对细胞适应性的影响.
- 在体内评估了aPKC在PDAC瘤生长中的作用.
主要成果:
- 确定了aPKCs (PKCζ和PKCι) 作为巨细胞瘤的新型调节剂.
- 证明细胞极性蛋白Par3和Par6对于PDAC细胞中谷氨酸压力诱导的巨皮诺细胞形成是必不可少的.
- 发现aPKCs通过EGFR或CREM信号促进巨细胞形成,导致Par3以dynein依赖的方式迁移到微管中.
- 表明aPKC的枯竭会损害细胞的健康状况,通过恢复巨型皮诺细胞形成来挽救这种状况.
- 确认aPKCs在体内支持PDAC生长.
结论:
- aPKCs是巨细胞细胞分裂的新型调节者,对于在代谢压力下PDAC细胞生存至关重要.
- 这项研究揭示了细胞极性蛋白在巨细胞细胞分裂调节中的不被重视的作用.
- 这些发现提高了对癌症代谢压力中巨细胞吸收的机制基础的理解.
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