PKM2 promotes cell migration and inhibits autophagy by mediating PI3K/AKT activation and contributes to the malignant development of gastric cancer
Abstract 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 expr...
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Nature Portfolio
2017-06-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-017-03031-1 |
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author | Chao Wang Jinling Jiang Jun Ji Qu Cai Xuehua Chen Yingyan Yu Zhenggang Zhu Jun Zhang |
author_facet | Chao Wang Jinling Jiang Jun Ji Qu Cai Xuehua Chen Yingyan Yu Zhenggang Zhu Jun Zhang |
author_sort | Chao Wang |
collection | DOAJ |
description | Abstract 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. |
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spelling | doaj.art-23d2295ff2db4daa815424bcfa67c5652022-12-21T21:20:27ZengNature PortfolioScientific Reports2045-23222017-06-017111410.1038/s41598-017-03031-1PKM2 promotes cell migration and inhibits autophagy by mediating PI3K/AKT activation and contributes to the malignant development of gastric cancerChao Wang0Jinling Jiang1Jun Ji2Qu Cai3Xuehua Chen4Yingyan Yu5Zhenggang Zhu6Jun Zhang7Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineAbstract 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.https://doi.org/10.1038/s41598-017-03031-1 |
spellingShingle | Chao Wang Jinling Jiang Jun Ji Qu Cai Xuehua Chen Yingyan Yu Zhenggang Zhu Jun Zhang PKM2 promotes cell migration and inhibits autophagy by mediating PI3K/AKT activation and contributes to the malignant development of gastric cancer Scientific Reports |
title | PKM2 promotes cell migration and inhibits autophagy by mediating PI3K/AKT activation and contributes to the malignant development of gastric cancer |
title_full | PKM2 promotes cell migration and inhibits autophagy by mediating PI3K/AKT activation and contributes to the malignant development of gastric cancer |
title_fullStr | PKM2 promotes cell migration and inhibits autophagy by mediating PI3K/AKT activation and contributes to the malignant development of gastric cancer |
title_full_unstemmed | PKM2 promotes cell migration and inhibits autophagy by mediating PI3K/AKT activation and contributes to the malignant development of gastric cancer |
title_short | PKM2 promotes cell migration and inhibits autophagy by mediating PI3K/AKT activation and contributes to the malignant development of gastric cancer |
title_sort | pkm2 promotes cell migration and inhibits autophagy by mediating pi3k akt activation and contributes to the malignant development of gastric cancer |
url | https://doi.org/10.1038/s41598-017-03031-1 |
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