通过p38介导的ACSL4酸化驱动通过Src基化引发的压力诱导的食道状细胞癌的生长
Qiang Yuan1,2,3,4, Yunshu Shi1,2,3,4, Junyong Wang3
1The Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
Nature communications
|April 8, 2025
概括
像热食物这样的外部刺激可以诱导食道状细胞癌 (ESCC). 研究表明p38激活ACSL4增强了酶活性,促进了癌症生长信号通路.
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:
- 食道状细胞癌 (ESCC) 与外部刺激 (如热食物和烟草) 有关.
- 在持续刺激下,驱动ESCC从正常表皮细胞向恶性瘤的进展的分子机制尚未完全理解.
研究的目的:
- 调查外部刺激引起的ESCC进展背后的分子机制.
- 确定关键的信号通路和参与ESCC瘤发生的分子参与者.
主要方法:
- 在ESCC进展中分析p38和ERK1/2激活.
- 在T679通过p38.8确定ACSL4酸化.
- 评估ACSL4的酶活性和myristoyl-CoA的产生.
- 评估Src基基化和下游ERK信号激活.
主要成果:
- 在ESCC进展过程中观察到p38和ERK1/2激活之间的正相关性.
- 通过p38确定了在T679处的ACSL4的酸化,增强了它的酶活性.
- 增加的myristoyl-CoA (C14:0 CoA) 生产是由于增强的ACSL4活性而导致的.
- 这一过程促进了Src基化,并激活了下游的ERK信号,从而促进了瘤的产生.
结论:
- 在ESCC中,ACSL4在调解压力诱导的信号通路方面发挥着作用.
- 在ESCC中,p38-ACSL4-myristoyl-CoA-Src-ERK通路有助于增长激活和瘤发生.
- 进一步阐明这些机制可能有助于早期癌症预防策略.
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