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通过激活JNK-ATF2/c-Jun-MMP-2/9轴,ANKRD49促进NSCLC的转移
Jia Sun1,2, Jin-Rui Hu3, Chao-Feng Liu1
1Department of Pulmonary and Critical Care Medicine, Shanxi Province Key Laboratory of Respiratory Disease, the First Hospital, Shanxi Medical University, NHC Key Laboratory of Pneumoconiosis, Taiyuan, Shanxi, 030001, China.
BMC cancer
|November 14, 2023
概括
安基林重复域49 (ANKRD49) 通过激活JNK信号,促进非小细胞肺癌 (NSCLC) 侵袭和转移,从而通过c-Jun和ATF2升调MMP-2/MMP-9表达. 这项研究澄清了ANKRD49的内容.
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:
- 安基林重复域49 (ANKRD49) 在肺腺癌 (LUAD) 和肺状癌 (LUSC) 中高度表达.
- ANKRD49在非小细胞肺癌 (NSCLC) 发病过程中的确切作用尚不清楚.
- 之前的研究表明,ANKRD49通过p38-ATF-2-MMP2/MMP9通路促进LUAD细胞入侵.
研究的目的:
- 用各种细胞系研究NSCLC中ANKRD49的功能和机制.
- 阐明NSCLC中ANKRD49调节的信号通路和分子点.
- 为了验证ANKRD49在NSCLC瘤性和体内转移中的作用.
主要方法:
- 实时qPCR评估ANKRD49在NSCLC组织和相邻的正常组织中的表达.
- 在体外测试 (过度表达,RNA干扰,凝组图,CCK-8,殖民地形成,伤口愈合,迁移,入侵) 在NCI-H1299和NCI-H1703细胞中.
- 免疫沉,染色体免疫沉和裸体小鼠模型用于分析分子相互作用,转录调节和瘤性.
主要成果:
- 与正常组织相比,NSCLC组织中的ANKRD49表达显著更高.
- ANKRD49过度表达通过增加MMP-2和MMP-9水平,增强NSCLC细胞的迁移和入侵.
- ANKRD49激活了JNK通路,导致c-Jun和ATF2酸化以及随后的MMP-2/MMP-9促进体的转录激活.
结论:
- ANKRD49通过通过c-Jun和ATF2通过JNK介导的MMP-2/MMP-9的转录激活促进NSCLC细胞入侵和转移2.
- 鉴定的分子机制不同于A549细胞中之前报告的途径,突出显示NSCLC异质性.
- 这项研究提供了对ANKRD49在NSCLC进展和转移中的作用的全面了解.
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