一个TGF-β-响应增强剂调节SRC表达和表皮质-介质细胞过渡相关的细胞迁移
Soshi Noshita1, Yuki Kubo1, Kentaro Kajiwara1
1Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Journal of cell science
|July 13, 2023
概括
转化生长因子-β (TGF-β) 通过增强剂上调SRC表达,促进癌症的入侵和转移. 这一途径涉及SMAD和JUN,这对上皮细胞-介质细胞过渡和细胞迁移至关重要.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 细胞信号传递 细胞信号传递
背景情况:
- 非受体氨酸激酶SRC在癌症中过度表达,导致侵袭和转移.
- 癌症中SRC上调的机制在很大程度上是未知的.
研究的目的:
- 阐明转化生长因子-β (TGF-β) 诱导SRC表达的机制.
- 研究TGF-β诱导的SRC上调在癌症进展中的作用.
主要方法:
- 利用MCF10A人类乳腺上皮细胞进行TGF-β1刺激.
- 进行染色体免疫沉 (ChIP) 测序以确定增强剂区域.
- 分析了SMAD和JUN在调节SRC表达中的作用.
主要成果:
- TGF-β通过激活内基性SRC增强剂,通过转录诱导SRC表达.
- TGF-β1上调SRC 1A促进体,增加SRC mRNA和蛋白质.
- SMAD复合体和JUN被招募到SRC增强剂中,调解TGF-β诱导的SRC表达.
- TGF-β诱导的SRC上调激活SRC-FAK电路,促进与EMT相关的细胞迁移.
结论:
- TGF-β信号驱动通过增强器激活SRC上调,有助于癌细胞入侵和转移.
- 已识别的TGF-β-SRC通路是特定的人类恶性瘤的潜在治疗标.
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