从TGF-β诱导的衰老逃脱促进了表皮性肝细胞癌细胞中的侵略性特征
Minenur Kalyoncu1, Dilara Demirci1, Sude Eris1,2
1Izmir Biomedicine and Genome Center, Turkey.
Molecular oncology
|March 14, 2025
概括
肝细胞癌 (HCC) 细胞可以逃脱转化生长因子-β (TGF-β) 诱导的衰老,发展耐药性. 这种可塑性通过改变细胞行为和信号通路来促进HCC的攻击性和转移.
科学领域:
- 癌症生物学 癌症生物学
- 分子瘤学分子瘤学
- 细胞衰老 细胞衰老
背景情况:
- 转化生长因子-β (TGF-β) 信号传递和细胞衰老对于肝细胞癌 (HCC) 的发展至关重要.
- 高的TGF-β活性矛盾地与HCC的攻击性相关,尽管它诱导了上皮细胞的衰老.
研究的目的:
- 研究HCC进展过程中二分法TGF-β功能和衰老调节之间的过渡.
- 了解HCC细胞发展TGF-β耐药性的机制.
主要方法:
- 在慢性TGF-β暴露实验中利用了上皮HCC细胞系Huh7.
- 评估了细胞表型,包括增殖,上皮细胞转移到介质细胞 (EMT),侵入性和转移.
- 分析了Smad分子激活和核贩运,转录组景观,并确定了关键调节器 (MARK1,GRM8).
主要成果:
- 慢性TGF-β暴露诱导了Smad3-介导衰老的逃脱,导致HCC细胞中的TGF-β抵抗.
- 耐药细胞表现出增加的增殖,EMT,侵入性和转移,与缺陷的Smad信号传递.
- 通过损害Smad活动动态,MARK1和GRM8被确定为TGF-β抗性的关键调节剂.
结论:
- 皮质HCC细胞可以利用衰老可塑性发展TGF-β耐药性,反对抗瘤反应.
- 这种现象有助于HCC向更具侵略性的表型和转移的进展.
- 这些发现揭示了HCC进展的新机制,包括衰老可塑性和TGF-β耐药性.
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