高血糖状态和流体剪切应力通过焦点粘附激酶影响转移性乳腺癌细胞迁移
bioRxiv : the preprint server for biology
|June 12, 2025
概括
高葡萄糖和流体剪切显著增强三阴性乳腺癌 (TNBC) 细胞迁移,由焦粘附激酶 (FAK) 介导. 这凸显了糖尿病如何促进乳腺癌转移.
科学领域:
- 生物医学工程 生物医学工程
- 癌症生物学 癌症生物学
- 内分泌学 在内分泌学.
背景情况:
- 糖尿病中常见的高血糖症与癌症风险增加和癌症进展有关.
- 三重阴性乳腺癌 (TNBC) 是高度攻击性和转移性.
- 癌细胞迁移受到生物物理微环境的影响,包括流体剪切应力.
研究的目的:
- 研究高葡萄糖和流体剪切应激对高度转移的TNBC细胞 (MDA-MB-231) 迁移的联合影响.
- 阐明焦粘附激酶 (FAK) 在调解这种反应中的作用.
- 探索糖尿病相关乳腺癌转移的潜在治疗点.
主要方法:
- 使用的MDA-MB-231 TNBC细胞和正常的MCF-10A细胞.
- 在生理流体剪切应力 (15 dyne/cm2) 下,细胞暴露在不同葡萄糖度 (5 mM 和 25 mM) 下.
- 评估细胞迁移使用伤愈合和博登室测试.
- 使用特定的FAK抑制剂研究了FAK的作用.
主要成果:
- 高葡萄糖 (25 mM) 在流体剪切应力 (15 dyne/cm2) 下显著增强了MDA-MB-231细胞迁移.
- 高葡萄糖和流体剪切对MDA-MB-231细胞的亲迁移效应被FAK抑制剂废除.
- 正常的MCF-10A细胞在流体剪切下显示出增加的迁移,无论葡萄糖水平如何.
结论:
- 高葡萄糖和流体剪切协同促进通过FAK激活TNBC细胞迁移.
- FAK在TNBC细胞感知和响应联合高血糖和流体剪切微环境方面发挥着关键作用.
- 这些发现为糖尿病加剧的乳腺癌转移提供了机制性的见解,并建议FAK作为潜在的治疗点.
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