化疗诱导的执行者卡斯帕酶激活通过表观遗传去抑制CDH12增加乳腺癌恶性病变
Yuxing Wang1, Ru Wang1, Xiaohe Liu1
1Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
Oncogenesis
|June 24, 2023
概括
癌细胞通过解体生存化学疗法获得增强的增殖和迁移. 这是由于加大素12 (CDH12) 表达的原因,为预防癌症复发提供了新的点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 癌症复发和转移是治疗中的重大挑战.
- 细胞亡,或编程细胞死亡,是消除癌细胞的关键机制.
- 执行者卡斯巴酶激活后细胞的生存,已经成为一种反机制.
研究的目的:
- 为了研究化学疗法后乳腺癌细胞中化的后果.
- 阐明驱动无性乳腺癌细胞增强恶性瘤的分子机制.
- 确定潜在的治疗点,以预防化疗后癌症复发.
主要方法:
- 乳腺癌细胞暴露于化疗药物.
- 在幸存的 (无性) 细胞中分析细胞增殖和细胞迁移.
- 研究基因表达的变化,专注于素12 (CDH12).
- 对CDH12促进体区域的表观遗传学分析 (DNA甲基化和基因组修饰).
- 评估包括ERK和CREB在内的信号通路.
主要成果:
- 经过化疗诱导的亡 (解体细胞) 幸存的乳腺癌细胞表现出增加的增殖和迁移.
- 卡德林12 (CDH12) 在异位细胞中显著上调.
- 通过激活ERK和CREB信号通路,CDH12促进乳腺癌恶性病变.
- 化疗诱导了DNA甲基化损失和CDH12促进体的抑制性基因素标记,导致其表达增加.
结论:
- 化疗后的阿纳斯塔斯增强了乳腺癌细胞恶性病因,通过上调CDH12.
- 在CDH12促进体的表观遗传变化对于这种持续的上调是至关重要的.
- 向CDH12或相关的表观遗传机制可能提供策略来打击癌症复发和转移.
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