补充调节蛋白CD46通过激活MMP9促进膀癌转移
Thuy Nguyen Thi1, Hien Duong Thanh1, Van-Tan Nguyen2
1Department of Anatomy, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
International journal of oncology
|June 7, 2024
概括
CD46通过增加MMP9表达来促进膀癌转移. 这涉及激活p38 MAPK和AKT通路,增强细胞入侵和扩散.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- CD46 (膜共因子蛋白) 保护细胞免受补充介导的损伤.
- CD46在各种癌症中失调,包括膀癌,在那里它促进免疫逃避.
- 它在癌症侵袭和转移中的作用不太清楚.
研究的目的:
- 研究CD46在膀癌细胞入侵和转移中的作用.
- 检查CD46对矩阵金属蛋白酶 (MMP) 的调节作用.
- 为了阐明参与CD46介导转移的信号通路.
主要方法:
- 在膀癌细胞系中分析CD46表达及其对MMP2和MMP9的影响.
- 研究CD46对p38 MAPK,AKT和激活蛋白1 (AP-1) 信号传递的影响.
- 功能性测试评估细胞迁移,入侵和体内转移.
- 药理上抑制p38的MAPK和AKT通路.
主要成果:
- 在膀癌细胞中,CD46过度表达与MMP9表达呈正相关性,但与MMP2无相关性.
- CD46触发了p38 MAPK和AKT的酸化,通过c-Jun.导致AP-1活动增加.
- 抑制p38 MAPK或AKT通路取消了CD46诱导的MMP9和AP-1上调.
- CD46诱导的MMP9上调增强了膀癌细胞的迁移,入侵和体内转移.
结论:
- CD46通过上调MMP9.9的调节,起到促进膀癌转移的作用.
- CD46介导的MMP9的促进包括p38 MAPK和AKT信号通路的激活.
- 向CD46或其下游途径可能提供抑制膀癌转移的治疗策略.
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