MST4通过激活MAPK-ERK信号通路调节炎症因子释放促进肝癌的侵袭和转移的机制研究

发布时间：2018-06-01 18:52

本文选题：丝氨酸/苏氨酸蛋白激酶 + 肝癌　；参考：《中国癌症杂志》2017年09期

【摘要】：背景与目的:丝氨酸/苏氨酸蛋白激酶4(mammalian Ste20-like kinase 4,MST4)促进肿瘤的侵袭和转移,前期研究发现,MST4可以通过上皮间质转化促进肝癌细胞的侵袭和转移。该研究旨在探讨MST4通过激活丝裂原活化蛋白激酶信号通路-细胞外信号调节激酶(mitogen-activated protein kinaseextracellular signal-regulated kinase,MAPK-ERK)信号通路影响炎症因子释放调节炎症微环境,促进肝癌的侵袭和转移。方法:采用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)方法对MST4高表达的肝癌细胞中白介素1β(interleukin-1β,IL-1β)、白介素6(interleukin-6,IL-6)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和趋化因子2(CC chemokine ligand-2,CCL2)的转录水平进行检查,通过蛋白[质]印迹法(Western blot)和酶联免疫吸附测定法(enzyme-linked immune sorbent assay,ELISA)研究MST4对肝癌细胞分泌炎症因子IL-1β、IL-6、TNF-α和CCL2蛋白量的表达及活性的影响。结果:MST4高表达的肝癌细胞,其IL-1β、IL-6、TNF-α和CCL2的转录水平、蛋白水平和分泌水平显著高于MST4低表达的肝癌细胞系(P0.05)。同时发现MST4可以通过改变ERK磷酸化的水平,促进细胞因子释放的改变。结论:MST4可以通过MAPK-ERK信号通路活化完成对肿瘤细胞分泌炎症因子的调节,促进炎症因子的分泌,增强肝癌细胞侵袭和转移的能力。
[Abstract]:Background & AIM: serine / threonine protein kinase (4(mammalian Ste20-like kinase 4) promotes tumor invasion and metastasis. The aim of this study was to investigate the effect of MST4 on inflammatory microenvironment by activating mitogen-activated protein kinaseextracellular signal-regulated kinases (MAPK-ERK) signaling pathway, and to promote the invasion and metastasis of hepatocellular carcinoma (HCC). Methods: the transcription levels of interleukin-1 尾 -interleukin-1 尾, tumor necrosis factor 伪 -tumor necrosis factor- 伪 (TNF- 伪) and chemokine 2(CC chemokine ligand-2CCL2 were detected by real-time fluorescent quantitative polymerase chain reaction- fluorescent quantitative polymerase chain Q-PCR assay in HCC cells with high expression of MST4. The effects of MST4 on the expression and activity of IL-1 尾 -IL-6 TNF- 伪 and CCL2 protein were studied by Western blot and enzyme linked immunosorbent assay (Elisa). Results the transcription, protein and secretion levels of IL-1 尾 -IL-6TNF- 伪 and CCL2 in the high expression of MST4 were significantly higher than those in the low expression of MST4 cell line (P0.05). It was also found that MST4 could promote cytokine release by changing the phosphorylation level of ERK. ConclusionMST4 can regulate the secretion of inflammatory cytokines by activation of MAPK-ERK signaling pathway, promote the secretion of inflammatory factors, and enhance the ability of invasion and metastasis of hepatoma cells.
【作者单位】：复旦大学附属肿瘤医院肝脏外科复旦大学上海医学院肿瘤学系;复旦大学附属华山医院普通外科;复旦大学附属肿瘤医院肿瘤内科复旦大学上海医学院肿瘤学系;
【基金】：国家自然科学基金青年项目(81602100) 上海市自然科学基金面上项目(12ZR1406200) 复旦大学附属肿瘤医院院级基金(2015-2017)
【分类号】：R735.7

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