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通过MAPK强化氨酸受体介导的释放是表皮转化和致癌的原因

Pengcheng Wang^1,2, Kristan H Cleveland¹, Ayaz Shahid¹

¹Department of Biotechnology and Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766.

Proceedings of the National Academy of Sciences of the United States of America

|December 10, 2025

概括

表皮生长因子 (EGF) 通过激活MAPK/ERK和瑞诺丁受体 (RyRs) 来促进皮肤癌,从而释放. 药物卡维迪洛尔通过向RyRs来抑制这一过程,从而提供了一个潜在的治疗策略.

科学领域:

细胞生物学细胞生物学
癌症研究癌症研究
药理学药理学是指药理学的学科.

背景情况:

皮表皮生长因子 (EGF) 通过MAPK/ERK通路促进皮肤细胞的生长和转变.
β阻断剂卡维迪洛尔抑制了EGF诱导的皮肤细胞转化,但其机制尚不清楚.
瑞诺丁受体 (RyRs) 参与信号传递和细胞过程.

研究的目的:

研究RyRs在EGF促进的皮肤细胞转化中的作用.
通过准RyRs来确定卡维迪洛是否抑制转化.
阐明MAPK/ERK,RyRs和释放在致癌过程中的相互作用.

主要方法:

使用JB6小鼠表皮细胞和一个RyR2-tdTomato记者小鼠模型.
评估了EGF诱导的ERK酸化和RyR2表达.
测量了4-chloro-m-cresol (4-CMC) 引起的释放和JB6细胞转化.
采用了RyR稳定剂,shRNA,卡维迪醇衍生物和体内紫外线辐射模型.

主要成果:

EGF上调RyR2和增强释放,这是由RyR稳定剂和MAPK/PLC抑制剂抑制的.
瑞R激动剂促进了JB6的转化,而瑞R稳定剂和胆阻断了它.
卡维迪醇对转化的抑制作用被 RyR shRNAs 取消,其衍生物的疗效与 RyR 抑制相关.
在体内,紫外线诱导的皮肤损伤因RyR激活而加剧,而在RyR2减少的小鼠中减弱.

结论:

由MAPK介导的RyR诱导的释放的增强是皮肤致癌的一个关键途径.
卡维迪洛尔通过向RyRs来抑制EGF促进的皮肤细胞转化,独立于其β-阻断活性.
针对RyR介导的信号传递,为皮肤癌的预防和治疗提供了潜在的治疗策略.

关键词:

JB6 P + 单元格中的 P + 单元格和是最重要的.癌症发生的原因是癌症发生.氨酸的受体是氨酸的受体.转化转化转化转化转化转化转化转化

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