敲低丙酮酸激酶M2（PKM2）可通过Wnt/β-连环蛋白信号通路调节上皮-间质转化，从而抑制人宫颈癌的肿瘤进展。
Knockdown of PKM2 suppresses tumor progression in human cervical cancer by modulating epithelial-mesenchymal transition via Wnt/β-catenin signaling.
作者信息
Lin Yanzhu, Meng Fanqing, Lu Zhiyuan, Chen Kai, Tao Yalan, Ouyang Yi, Cao Xinping
机构信息
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China,
Department of Anesthesiology, Jinan Maternity and Child Care Hospital, Jinan, China.
出版信息
Cancer Manag Res. 2018 Oct 4;10:4191-4202. doi: 10.2147/CMAR.S178219. eCollection 2018.
BACKGROUND
Pyruvate kinase isozyme type M2 (PKM2) is a key glycolytic enzyme and is upregulated in multiple human malignancies. However, the role of PKM2 in human cervical cancer (CC) remains elusive. Thus, this study explored the role of PKM2 in CC by detecting its expression patterns in human CC tissues and cell lines and investigated its effects on cell proliferation and invasion.
MATERIALS AND METHODS
Quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemistry and western blotting assays were used to detect the expression of PKM2 in CC tissues and CC cells. In vitro, we overexpressed and knocked down PKM2 expression in CC cell lines and investigated the biological function and underlying mechanism of PKM2 in cervical carcinogenesis.
RESULTS
The results showed that PKM2 mRNA and protein were highly expressed in CC tissues and cell lines. Furthermore, increasing PKM2 expression was closely correlated with the clinical stage (=0.001) and lymph node metastasis (=0.023). The functional roles of PKM2 were determined using Cell Counting Kit-8, colony formation, and transwell assays. The results showed that PKM2 knockdown inhibited cell proliferation and the migratory and invasive capacities of CC cells, suppressed epithelial-mesenchymal transition (EMT), and inhibited Wnt/β-catenin signaling in vitro. However, overexpression of PKM2 led to increased proliferation and invasion activity as well as the EMT in CC cells.
CONCLUSION
Taken together, our study results revealed that PKM2 may act as a molecular target for CC treatment.
背景
丙酮酸激酶M2型同工酶（PKM2）是一种关键的糖酵解酶，在多种人类恶性肿瘤中上调。然而，PKM2在人类宫颈癌（CC）中的作用仍不清楚。因此，本研究通过检测其在人类CC组织和细胞系中的表达模式，探讨了PKM2在CC中的作用，并研究了其对细胞增殖和侵袭的影响。
材料与方法
采用定量逆转录聚合酶链反应（qRT-PCR）、免疫组织化学和蛋白质印迹分析检测PKM2在CC组织和CC细胞中的表达。在体外，我们在CC细胞系中过表达和敲低PKM2表达，并研究PKM2在宫颈癌发生中的生物学功能和潜在机制。
结果
结果显示，PKM2 mRNA和蛋白在CC组织和细胞系中高表达。此外，PKM2表达增加与临床分期（=0.001）和淋巴结转移（=0.023）密切相关。使用细胞计数试剂盒-8、集落形成和Transwell分析确定了PKM2的功能作用。结果表明，敲低PKM2可抑制CC细胞的增殖、迁移和侵袭能力，抑制上皮-间质转化（EMT），并在体外抑制Wnt/β-连环蛋白信号通路。然而，PKM2的过表达导致CC细胞的增殖和侵袭活性增加以及EMT。
结论
综上所述，我们的研究结果表明PKM2可能作为CC治疗的分子靶点。
Zotero 插件