细胞外基质刚度通过HSF4调节结直肠癌的进展
Kangtao Wang1,2, Siyi Ning3, Shuai Zhang1
1Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Journal of experimental & clinical cancer research : CR
|January 29, 2025
概括
瘤硬性和热冲击转录因子4 (HSF4) 通过调节EMT通路,促进结直肠癌 (CRC) 的进展和转移. 准硬度和HSF4可能会改善CRC的预后和治疗.
科学领域:
- 在瘤学瘤学.
- 生物物理学的生物物理.
- 分子生物学分子生物学
背景情况:
- 大肠直肠癌 (CRC) 的发病率和死亡率很高,晚期预后不佳.
- 瘤微环境的作用,特别是细胞外矩阵 (ECM) 硬性,在CRC转移中的作用仍然不清楚.
- 了解这些因素对于改善诊断和治疗策略至关重要.
研究的目的:
- 研究瘤微环境硬度对结直肠癌 (CRC) 进展和转移的影响.
- 为了确定关键的分子参与者,如热冲击转录因子4 (HSF4),涉及性驱动的CRC进步.
- 评估瘤硬性和HSF4作为CRC的预后和治疗点的潜力.
主要方法:
- 使用磁共振弹性学 (MRE) 评估瘤刚度,并通过107名CRC患者的马森染色测定评估原蛋白含量.
- 利用在不同度的矩阵上培养的CRC细胞上的转录组测序来识别与度相关的基因.
- 在不同的ECM刚性条件下生成HSF4淘汰CRC细胞模型,以评估其在增殖,迁移和入侵中的作用,在体外和体内.
主要成果:
- 瘤硬度明显高于正常组织,与原含量和TNM阶段有积极的相关性.
- 高度矩阵改变了细胞功能和信号通路;高HSF4表达与瘤度和不良预后相关.
- HSF4淘汰抑制了CRC细胞的增殖,迁移和入侵,特别是在刚性基质上,体内研究证实HSF4在瘤生长和转移中的作用.
结论:
- 瘤硬性通过通过HSF4.4调节EMT相关的信号通路促进CRC增殖和转移.
- 瘤硬度和HSF4被确定为CRC预后评估的潜在生物标志物.
- 向瘤硬性和HSF4为结直肠癌的治疗干预提供了一个有希望的途径.
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