Knockdown of PKM2 Suppresses Tumor Growth and Invasion in Lung Adenocarcinoma

International Journal of Molecular Sciences

Hong Sun²  Anyou Zhu²  Lunjun Zhang²  Jie Zhang¹  Zhengrong Zhong²  Fengchao Wang² 

[1] Department of Pathology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, China; E-Mail:;Department of Clinical Laboratory Science, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; E-Mails:

关键词: lung adenocarcinoma;    pyruvate kinase M2;    glycolysis;    fatty acid synthesis;    invasion;   

DOI  :  10.3390/ijms161024574

来源: mdpi

【 摘 要 】

Accumulating evidence shows that activity of the pyruvate kinase M2 (PKM2) isoform is closely related to tumorigenesis. In this study, we investigated the relationship betweenPKM2 expression, tumor invasion, and the prognosis of patients with lung adenocarcinoma. We retrospectively analyzed 65 cases of patients with lung adenocarcinoma who were divided into low and a high expression groups based on PKM2immunohistochemical staining. High PKM2 expression was significantly associated with reduced patient survival. We used small interfering RNA (siRNA) technology to investigate the effect of targeted PKM2-knockout on tumor growth at the cellular level. In vitro, siRNA-mediated PKM2-knockdown significantly inhibited the proliferation, glucose uptake (25%), ATP generation (20%) and fatty acid synthesis of A549 cells, while the mitochondrial respiratory capacity of the cells increased (13%).Western blotting analysis showed that PKM2-knockout significantly inhibited the expression of the glucose transporter GLUT1 and ATP citrate lyase, which is critical for fatty acid synthesis. Further Western blotting analysis showed that PKM2-knockdown inhibited the expression of matrix metalloproteinase 2 (MMP-2) and vascular endothelial growth factor (VEGF), which are important in degradation of the extracellular matrix and angiogenesis, respectively. These observations show that PKM2 activates both glycolysis and lipid synthesis, thereby regulating cell proliferation and invasion. This information is important in elucidating the mechanisms by which PKM2 influences the growth and metastasis of lung adenocarcinoma at the cellular and molecular level, thereby providing the basic data required for the development of PKM2-targeted gene therapy.

【 授权许可】

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© 2015 by the authors; licensee MDPI, Basel, Switzerland.