通道TRPC6通过调节整合素α6mRNA拼接来促进化疗诱导的持久性
Dimpi Mukhopadhyay1, Hira Lal Goel1, Choua Xiong1
1Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Cell reports
|November 1, 2023
概括
暂时受体潜在通道6 (TRPC6) 通过调节整合素α6拼接,驱动乳腺癌干细胞的化疗耐药性. 抑制TRPC6使瘤对治疗重新敏感,提供了一个新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 了解治疗后瘤细胞持久性的机制对于治疗复发性疾病至关重要.
- 乳腺癌干细胞对化疗有抗性,有助于复发.
研究的目的:
- 研究短暂受体潜在通道6 (TRPC6) 在乳腺癌干细胞特性和化疗耐药性的作用.
- 阐明TRPC6有助于治疗后瘤细胞持久性的分子机制.
主要方法:
- 研究了TRPC6在乳腺癌干细胞中的功能.
- 分析了TRPC6介导的输入及其对整合素α6mRNA拼接的影响.
- 评估TRPC6抑制对瘤细胞干细胞,持久性和化疗敏感性的 in vitro 和 in vivo 影响.
主要成果:
- TRPC6调解的进入,促进乳腺癌干细胞的特性,包括耐化疗.
- TRPC6通过抑制上皮质拼接调节蛋白1 (ESRP1) 调节整合素α6 mRNA拼接,从而导致整合素α6B变体表达.
- TRPC6和整合素alpha6B激活TAZ,抑制Myc,这有助于癌症干和持久性.
- 治疗性抑制TRPC6使三阴性乳腺癌 (TNBC) 细胞和瘤对化疗敏感.
结论:
- TRPC6是乳腺癌中化疗诱导的持久性的一个关键媒介,通过整合蛋白mRNA拼接起作用.
- 向TRPC6提供了一种潜在的治疗策略,以克服化疗耐药性并改善TNBC的治疗结果.
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