PKM2促进肿瘤发展的作用机制研究

The Mechanisms of PKM2 Promoting Tumor Progression

为了分析丙酮酸激酶M2型(pyruvate kinase M2,PKM2)在不同肿瘤中的表达情况及其与肿瘤患者临床预后的关系,并探索PKM2对肿瘤细胞增殖和迁移的影响及其作用机制,用TCGA数据库和免疫印迹分析了33种肿瘤中PKM2的表达情况,探索了PKM2与不同肿瘤患者预后的关系。在肺癌细胞系中过表达PKM2,利用CCK8和Transwell方法分析PKM2对肺癌细胞增殖和迁移能力的影响。利用免疫印迹检测不同肿瘤细胞中过表达和敲低PKM2对热休克蛋白90α(Hsp90α)分泌的影响以及上皮-间质转化(epithelial-mesenchgmal transition,EMT)相关蛋白的变化。TCGA数据分析显示,PKM2在包括乳腺癌、肺癌等15种肿瘤中高表达,且9种肿瘤中PKM2的高表达与肿瘤的预后具有显著相关性。在肺癌细胞中过表达PKM2后,肺癌细胞的增殖和迁移能力显著增强。过表达PKM2能够显著增加乳腺癌和肺癌中Hsp90α的分泌。敲低PKM2能够抑制N-钙黏蛋白(N-cadhesion)和波形蛋白(Vimentin)的表达,促进E-钙黏蛋白(E-cadhesion)的表达。研究结果表明,PKM2在多种肿瘤中高表达且与肿瘤预后显著相关,能够通过影响Hsp90α的分泌以及上皮-间质转化相关蛋白的表达从而促进肿瘤的进展。PKM2有望成为潜在的广谱肿瘤标志物和治疗靶点。

To investigate the expression of pyruvate kinase M2(PKM2)in different tumor tissue and its relationship with the clin⁃ical prognosis of cancer patients,and to explore the effects of PKM2 on tumor cell proliferation and migration and its mechanism of action,TCGA database and immunoblotting were used to analyze the expression of PKM2 in 33 tumors.The relationship be⁃tween PKM2 and the prognosis of different tumor patients was explored.PKM2 was overexpressed in lung cancer cell lines,and the effect of PKM2 on lung cancer cell proliferation and migration were explored by CCK8 and Transwell assay.The effect of PKM2 overexpression on heat shock protein 90 alpha(Hsp90α)secretion in different tumor cells was detected by immunoblot⁃ting.Key proteins in the EMT process were detected after PKM2 knockdown.PKM2 was found highly expressed in 15 tumors,in⁃cluding breast cancer and lung cancer,and the high expression of PKM2 in 9 tumors was significantly correlated with the progno⁃sis of tumors.After the expression of PKM2,the proliferation and migration ability of lung cancer cells was significantly en⁃hanced.Overexpression of PKM2 could significantly increase Hsp90αsecretion in breast cancer and lung cancer.Knocking down PKM2 could inhibit the expression of N-cadherin and Vimentin and increase the expression of E-cadherin.Results showed that,PKM2 was highly expressed in a variety of tumors and was significantly correlated with tumor prognosis.PKM2 could promote tu⁃mor progression by affecting the secretion of Hsp90αand the levels of epithelial-mesenchymal transition(EMT)related proteins.PKM2 may be a potential broad-spectrum tumor marker and therapeutic target.