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Knockdown of PKM2 Suppresses Tumor Growth and Invasion in Lung Adenocarcinoma

التفاصيل البيبلوغرافية
العنوان: Knockdown of PKM2 Suppresses Tumor Growth and Invasion in Lung Adenocarcinoma
المؤلفون: Hong Sun, Anyou Zhu, Lunjun Zhang, Jie Zhang, Zhengrong Zhong, Fengchao Wang
المصدر: International Journal of Molecular Sciences, Vol 16, Iss 10, Pp 24574-24587 (2015)
بيانات النشر: MDPI AG, 2015.
سنة النشر: 2015
المجموعة: LCC:Biology (General)
LCC:Chemistry
مصطلحات موضوعية: lung adenocarcinoma, pyruvate kinase M2, glycolysis, fatty acid synthesis, invasion, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1422-0067
Relation: http://www.mdpi.com/1422-0067/16/10/24574; https://doaj.org/toc/1422-0067
DOI: 10.3390/ijms161024574
URL الوصول: https://doaj.org/article/611158ede7554563a8f655f33add692a
رقم الأكسشن: edsdoj.611158ede7554563a8f655f33add692a
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:14220067
DOI:10.3390/ijms161024574