由HSF1重新编程瘤侧膜是恶性瘤的强有力的推动者
Ruth Scherz-Shouval1, Sandro Santagata2, Marc L Mendillo1
1Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Cell
|August 2, 2014
概括
热冲击因子1 (HSF1) 对癌症相关纤维细胞 (CAFs) 的重编程支持瘤进展. 这种由CAF驱动的程序与癌细胞不同,增强恶性瘤并预测早期癌症患者的不良结果.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 瘤微环境的 stromal 细胞对于癌症的进展和转移至关重要.
- 驱动树皮细胞转录重编程的因素在很大程度上仍未知.
- 热冲击因子1 (HSF1) 是一种转录调节剂,在细胞应激反应中具有已知的作用.
研究的目的:
- 研究HSF1在癌症相关纤维细胞 (CAF) 中的作用.
- 阐明在CAF中由HSF1驱动的转录程序.
- 为了确定癌症中肌层HSF1激活的临床意义.
主要方法:
- 在瘤组织内的CAF中分析HSF1激活.
- 具有和没有HSF1激活的CAF的转录概况.
- 侧膜HSF1激活与早期乳腺癌和肺癌患者结局的相关性分析.
主要成果:
- 在CAF中,HSF1经常被激活,并作为恶性瘤的强有力的激活剂.
- HSF1驱动一个独特的CAF转录程序,该程序支持恶性瘤非细胞自主.
- 流体HSF1激活与早期乳腺癌和肺癌患者的不良结果密切相关.
- 关键的树叶信号分子TGF-β和SDF1在这个过程中起着关键的作用.
结论:
- 瘤劫持HSF1的生存功能,通过细胞自主和非细胞自主机制促进恶性瘤.
- 针对CAF中的HSF1是一种潜在的治疗策略.
- 了解HSF1在瘤微环境中的作用具有重要的治疗意义.
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