PKM2 promotes cell migration and inhibits autophagy by mediating PI3K/AKT activation and contributes to the malignant development of gastric cancer

• Published in: Scientific reports Vol. 7; no. 1; pp. 2886 - 14
• Main Authors: Wang, Chao, Jiang, Jinling, Ji, Jun, Cai, Qu, Chen, Xuehua, Yu, Yingyan, Zhu, Zhenggang, Zhang, Jun
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 06.06.2017; Nature Publishing Group UK; Nature Portfolio
• Subjects: 1-Phosphatidylinositol 3-kinase; Aged; Aged, 80 and over; AKT protein; Animal models; Animals; Autophagy - genetics; Carrier Proteins - genetics; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Disease Progression; Female; Gastric cancer; Gene Expression; Gene Knockdown Techniques; Glycolysis; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; Membrane Proteins - genetics; Metastases; Mice; Middle Aged; Models, Biological; Neoplasm Metastasis; Neoplasm Staging; Phagocytosis; Phosphatidylinositol 3-Kinases - metabolism; Prognosis; Proto-Oncogene Proteins c-akt - metabolism; Pyruvate kinase; Pyruvic acid; Ribonucleic acid; RNA; Signal Transduction; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Thyroid Hormone-Binding Proteins; Thyroid Hormones - genetics; Tumor Burden; Tumorigenicity; Xenografts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-03031-1

Pyruvate kinase M2 (PKM2) is a key kinase of glycolysis and is characteristic of all proliferating cells. The role of PKM2 in gastric cancer (GC) is still ambiguous and yet to be determined. To better understand the role of PKM2 in both the migration and invasion of GC, we measured the expression of PKM2 in GC cell lines using qRT-PCR and western blot. The prognostic value of PKM2 was analyzed by Immunohistochemistry in a cohort containing 88 GC patients. PKM2 was knocked down by the short hairpin RNA plasmid vector in NCI-N87 and BGC-823 cells, and the biological behavior and downstream signaling pathways were also investigated in vitro. Subcutaneous xenografts and pulmonary metastases models were constructed in nude mice to compare the differences in tumorgenesis and metastasis after Knockdown of PKM2. Our results obtained from in vitro cell biological behavior, in vivo tumorigenicity studies, and primary GC samples revealed an oncogenic role for PKM2 in GC. Furthermore, for those GC patients who received radical resection, PKM2 might serve as a novel prognostic biomarker and target which would allow for a brand new treatment strategy for GC in the clinical settings.