PFKFB4对胃癌细胞侵袭和迁移能力的影响及其作用

doi:10.11904/j.issn.1002-3070.2020.01.007

摘要/Abstract

摘要： 目的探讨激酶PFKFB4是否参与调控胃癌细胞侵袭和迁移并对其作用机理进行初步研究。方法使用免疫共沉淀检测与PFKFB4有相互作用的SRC家族蛋白,通过转录组测序寻找下游调控基因,利用Western blot和qRT-PCR验证下游基因与磷酸化SRC蛋白的关系,并通过Transwell方法检测PFKFB4相关通路对胃癌细胞迁移和侵袭能力的影响。结果 PFKFB4能够与SRC-2相互作用,但PFKFB4不影响SRC-2的表达,而是磷酸化SRC-2第698位的丝氨酸;SRC-2 Ser698磷酸化后,其下游调控基因LKB1的mRNA和蛋白的表达水平都受到抑制,同时胃癌细胞的迁移和侵袭能力增强。结论 PFKFB4通过磷酸化SRC-2负调控抑癌因子LKB1的表达增强胃癌细胞的迁移和侵袭能力。

关键词: PFKFB4, 磷酸化, SRC-2, 胃癌细胞, 侵袭, 迁移

Abstract: Objective The Objective of this study was to investigate whether kinase PFKFB4 was involved in the regulating invasion and migration of gastric cancer cells and its mechanism of action.Methods The SRC family proteins interacting with PFKFB4 were detected by immunoprecipitation.The downstream regulatory genes were identified by transcriptome sequencing.The relationship between downstream genes and phosphorylated SRC proteins was verified by Western blot and qRT-PCR.The effect of PFKFB4 related to pathway on abilities of migration and invasion was detected in gastric cancer cells by Transwell assay.Results PFKFB4 could interact with SRC-2.The expression of SRC-2 was not affected by PFKFB4.But PFKFB4 could phosphorylate serine at site 698 of SRC-2.After phosphorylation of SRC-2 Ser698,downstream regulatory gene-LKB1 at levels of mRNA and protein was down-regulated.As a result,the migration and invasion ability of gastric cancer cells was enhanced.Conclusion PFKFB4 negatively regulates the expression of tumor suppressor gene-LKB1 by phosphorylation of SRC-2,and enhances the migration and invasion of gastric cancer cells.

Key words: PFKFB4, Phosphorylation, SRC-2, Gastric cancer cells, Invasion, Migration

中图分类号:

R735.2

王鸣, 孙梯业. PFKFB4对胃癌细胞侵袭和迁移能力的影响及其作用[J]. 实用肿瘤学杂志, 2020, 34(1): 37-42.

WANG Ming, SUN Tiye. Effects of PFKFB4 on invasion and migration of gastric cancer cells and its mechanism[J]. Journal of Practical Oncology, 2020, 34(1): 37-42.

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