胰腺RECK无活化促进癌症的形成,上皮细胞-介质细胞过渡,以及转移
Tomonori Masuda1, Akihisa Fukuda1, Go Yamakawa1
1Department of Gastroenterology and Hepatology.
The Journal of clinical investigation
|September 15, 2023
概括
雷克蛋白损失在小鼠中加速胰腺癌 (PDAC),促进转移并降低存活率. 恢复Reck抑制癌细胞入侵和上皮细胞-介质细胞过渡,表明其瘤抑制作用.
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:
- 在人类癌症中,RECK (具有卡扎尔基因的逆转诱导氨酸丰富蛋白) 经常被下调.
- 雷克失活在致癌过程中的确切作用,特别是在胰腺管腺癌 (PDAC) 中,仍然在很大程度上未被定义.
研究的目的:
- 研究RECK失活对PDAC发育和进展的功能影响.
- 阐明RECK影响PDAC表型和转移的分子机制.
主要方法:
- 利用一种基因工程小鼠模型的PDAC与胰腺Reck删除.
- 采用血统追踪,脏移植试验和分子分析 (基因表达,蛋白质水平).
- 在人类PDAC样本中,与临床病理特征相关的RECK表达.
主要成果:
- 胰腺REC删除显著加快了自发PDAC的发展,其特点是介质细胞表型,肝转移增加,生存率降低.
- 在PDAC细胞中,REC删除诱导了表皮质-介质细胞过渡 (EMT),产生与癌症相关的纤维细胞样细胞.
- RECK重新表达抑制了MMP2/MMP3,增加了E-cadherin,并降低了促进EMT的转录因子,降低了转移潜力.
- 人类PDAC中的低RECK表达与差异化,转移和更差的预后相关.
结论:
- 在胰腺癌中,RECK作为瘤抑制剂起作用.
- 通过EMT,RECK的失活促进了PDAC的进展和转移.
- 雷克具有作为人类PDAC治疗点的潜力.
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