丙酮酸激酶M2通过活化信号转导和转录激活因子3影响皮肤鳞状细胞癌上皮间质转化过程  

Pyruvate kinase M2 regulates epithelial-mesenchymal transition of cutaneous squamous cell carcinoma by activating STAT3

作　　者：刘念念 缪旭[1] 施健[1] 张冬梅 张俐 陈赛 LIU Niannian;MIAO Xu;SHI Jian;ZHANG Dongmei;ZHANG Li;CHEN Sai(Department of Dermatology,the Second Affiliated Hospital of Nantong University,Nantong 226014,China;Medical Research Center,the Second Affiliated Hospital of Nantong University,Nantong 226014,China)

机构地区：[1]南通大学第二附属医院皮肤科,江苏南通226014 [2]南通大学第二附属医院临床研究中心,江苏南通226014

出　　处：《临床皮肤科杂志》2023年第11期652-660,共9页Journal of Clinical Dermatology

基　　金：南通市市级科技计划项目(MSZ18092);2021年度南通市卫生健康委员会科研立项课题(MB2021019)。

摘　　要：目的:检测丙酮酸激酶(PK)M2和磷酸化信号转导和转录激活因子(p-STAT)3在皮肤鳞状细胞癌(CSCC)中的表达情况,初步探讨其在CSCC A431细胞系上皮间质转化过程中的作用机制。方法:选取经组织病理检查确诊的30例CSCC患者肿瘤组织和10例行皮肤美容手术患者术中修整切除的正常皮肤组织,通过免疫组化SP法比较PKM2和p-STAT3在两种组织中的表达情况。分析CSCC中PKM2和p-STAT3表达水平与临床病理资料的相关性。采用慢病毒感染法构建靶向敲低PKM2基因的CSCC A431细胞模型,采用免疫印迹(Western blot)法验证敲低模型的构建效果。通过Transwell实验和细胞划痕实验探讨PKM2对A431细胞迁移能力的影响。采用Western blot法检测STAT3、p-STAT3(Tyr705)、N-cadherin、Vimentin和Slug蛋白的表达。结果:PKM2和p-STAT3在CSCC中均高表达,且两者表达水平之间呈正相关。PKM2和p-STAT3在CSCC中的表达与肿瘤分化程度相关。在A431细胞中敲低PKM2基因后,p-STAT3(Tyr705)、N-cadherin和Slug表达下降,差异有统计学意义(P<0.05),而STAT3和Vimentin表达变化差异无统计学意义。结论:PKM2和p-STAT3的高表达可能参与了CSCC的发生及发展,且PKM2可能通过活化STAT3促进CSCC上皮间质转化过程。Objective:To detect the expression of pyruvate kinase(PK)M2 and phosphorylated signal transducer and activator of transcription(p-STAT)3 in cutaneous squamous cell carcinoma(CSCC),and to explore the mechanism of PKM2 in epithelial-mesenchymal transition(EMT)of cutaneous squamous cell carcinoma.Methods:The expression levels of PKM2 and p-STAT3 in 30 cases of pathologically confirmed CSCC and 10 cases of normal skin tissues(repaired by skin cosmetic surgery)were detected with immunohistochemistry.The correlation between the expression of PKM2 and p-STAT3 in CSCC and clinicopathological data was analyzed.The cutaneous squamous cell carcinoma A431 cell line model was constructed through knocking down PKM2 using lentivirus.The knockdown efficiency of PKM2 was confirmed by Western blot.Transwell assay and Wound-healing assay were used to explore PKM2 effect on the migration of A431 cells.Western blot was used to examine the expression levels of STAT3,p-STAT3(Tyr705),N-cadherin,Vimentin and Slug.Results:PKM2 and p-STAT3 were highly expressed in CSCC,and there was a positive correlation between their expression levels.The expression of PKM2 and p-STAT3 in CSCC was related to the degree of tumor differentiation.The knockdown of PKM2 inhibited the expression of p-STAT3(Tyr705),N-cadherin and Slug.Meanwhile,the expression levels of STAT3 and Vimentin were not significantly changed.Conclusion:The high expression of PKM2 and p-STAT3 may be involved in the development of cutaneous squamous cell carcinoma,and PKM2 promotes the EMT of cutaneous squamous cell carcinoma by activating STAT3.

关 键 词：丙酮酸激酶M2 皮肤鳞状细胞癌 上皮间质转化 信号转导和转录激活因子3 

分 类 号：R739.5[医药卫生—肿瘤]