由TGFβ对ΔNp63和TAp63的复杂和可变调节对状细胞上皮质到介质细胞过渡的动态有影响
Zuzana Pokorná1,2, Zuzana Tylichová1, Borivoj Vojtesek1
1Research Center of Applied Molecular Oncology (RECAMO), Masaryk Memorial Cancer Institute, Zluty Kopec 7, 656 53, Brno, Czech Republic.
Scientific reports
|March 28, 2024
概括
转化生长因子β (TGFβ) 选择性地影响状细胞中的ΔNp63蛋白,影响表皮细胞转化为介质细胞 (EMT) 和状细胞癌 (SCC) 的癌症进展. 这揭示了具有治疗意义的复杂TGFβ-p63相互作用.
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:
- 转化生长因子β (TGFβ) 在炎症,伤口愈合,上皮转化为介质细胞 (EMT) 和癌症干细胞生物学中至关重要.
- 状细胞癌 (SCC) 的特点是高的ΔNp63水平,维持上皮表型和状干细胞.
- ΔNp63和TGFβ信号之间的相互作用是复杂的,以前报告的效果是矛盾的.
研究的目的:
- 研究TGFβ对非恶性状和SCC细胞中的p63异型蛋白和mRNA的影响.
- 确定正规与非正规TGFβ信号通路在这些相互作用中的作用.
主要方法:
- 用TGFβ治疗非恶性角质细胞和SCC细胞.
- 对p63异型蛋白和mRNA水平的分析.
- 评估SMAD3激活和TGFβ受体抑制以界定信号通路.
主要成果:
- 在非恶性角质细胞中,TGFβ通过规范性TGFβ通路信号传导 (SMAD3激活) 选择性地增加了ΔNp63蛋白.
- TP63异形mRNAs表现出动态变化,最初增加,随后减少,显示出与蛋白质水平的不一致.
- TGFβ的影响取决于状细胞中正规的TGFβ途径异常的程度.
结论:
- TGFβ对状细胞中的p63异型具有复杂而异质的作用,由正规的TGFβ通路活性调节.
- TGFβ和p63之间的相互作用会影响SCC中的EMT状态.
- 了解这种相互作用对SCC瘤进展和治疗策略具有重大临床影响.
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