Metabolic protein phosphoglycerate kinase 1 confers lung cancer migration by directly binding HIV Tat specific factor 1
Abstract Phosphoglycerate kinase (PGK) is involved in glycolytic and various metabolic events. Dysfunction of PGK may induce metabolic reprogramming and the Warburg effect. In this study, we demonstrated that PGK1, but not PGK2, may play a key role in tumorigenesis and is associated with metastasis....
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2021-06-01
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Series: | Cell Death Discovery |
Online Access: | https://doi.org/10.1038/s41420-021-00520-1 |
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doaj-cc822012d3b84dc1b3a5d679e30258322021-06-06T11:50:31ZengNature Publishing GroupCell Death Discovery2058-77162021-06-017111510.1038/s41420-021-00520-1Metabolic protein phosphoglycerate kinase 1 confers lung cancer migration by directly binding HIV Tat specific factor 1Yu-Chan Chang0Ming-Hsien Chan1Chien-Hsiu Li2Chih-Jen Yang3Yu-Wen Tseng4Hsing-Fang Tsai5Jean Chiou6Michael Hsiao7Deparment of Biomedical Imaging and Radiological Sciences, National Yang-Ming UniversityGenomics Research Center, Academia SinicaGenomics Research Center, Academia SinicaDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityGenomics Research Center, Academia SinicaGenomics Research Center, Academia SinicaGenomics Research Center, Academia SinicaGenomics Research Center, Academia SinicaAbstract Phosphoglycerate kinase (PGK) is involved in glycolytic and various metabolic events. Dysfunction of PGK may induce metabolic reprogramming and the Warburg effect. In this study, we demonstrated that PGK1, but not PGK2, may play a key role in tumorigenesis and is associated with metastasis. We observed an inverse correlation between PGK1 and the survival rate in several clinical cohorts through bioinformatics statistical and immunohistochemical staining analyses. Surprisingly, we found that PGK1 was significantly increased in adenocarcinoma compared with other subtypes. Thus, we established a PGK1-based proteomics dataset by a pull-down assay. We further investigated HIV-1 Tat Specific Factor 1 (HTATSF1), a potential binding partner, through protein–protein interactions. Then, we confirmed that PGK1 indeed bound to HTATSF1 by two-way immunoprecipitation experiments. In addition, we generated several mutant clones of PGK1 through site-directed mutagenesis, including mutagenesis of the N-terminal region, the enzyme catalytic domain, and the C-terminal region. We observed that even though the phosphoglycerate kinase activity had been inhibited, the migration ability induced by PGK1 was maintained. Moreover, our immunofluorescence staining also indicated the translocation of PGK1 from the cytoplasm to the nucleus and its colocalization with HTATSF1. From the results presented in this study, we propose a novel model in which the PGK1 binds to HTATSF1 and exerts functional control of cancer metastasis. In addition, we also showed a nonenzymatic function of PGK1.https://doi.org/10.1038/s41420-021-00520-1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yu-Chan Chang Ming-Hsien Chan Chien-Hsiu Li Chih-Jen Yang Yu-Wen Tseng Hsing-Fang Tsai Jean Chiou Michael Hsiao |
spellingShingle |
Yu-Chan Chang Ming-Hsien Chan Chien-Hsiu Li Chih-Jen Yang Yu-Wen Tseng Hsing-Fang Tsai Jean Chiou Michael Hsiao Metabolic protein phosphoglycerate kinase 1 confers lung cancer migration by directly binding HIV Tat specific factor 1 Cell Death Discovery |
author_facet |
Yu-Chan Chang Ming-Hsien Chan Chien-Hsiu Li Chih-Jen Yang Yu-Wen Tseng Hsing-Fang Tsai Jean Chiou Michael Hsiao |
author_sort |
Yu-Chan Chang |
title |
Metabolic protein phosphoglycerate kinase 1 confers lung cancer migration by directly binding HIV Tat specific factor 1 |
title_short |
Metabolic protein phosphoglycerate kinase 1 confers lung cancer migration by directly binding HIV Tat specific factor 1 |
title_full |
Metabolic protein phosphoglycerate kinase 1 confers lung cancer migration by directly binding HIV Tat specific factor 1 |
title_fullStr |
Metabolic protein phosphoglycerate kinase 1 confers lung cancer migration by directly binding HIV Tat specific factor 1 |
title_full_unstemmed |
Metabolic protein phosphoglycerate kinase 1 confers lung cancer migration by directly binding HIV Tat specific factor 1 |
title_sort |
metabolic protein phosphoglycerate kinase 1 confers lung cancer migration by directly binding hiv tat specific factor 1 |
publisher |
Nature Publishing Group |
series |
Cell Death Discovery |
issn |
2058-7716 |
publishDate |
2021-06-01 |
description |
Abstract Phosphoglycerate kinase (PGK) is involved in glycolytic and various metabolic events. Dysfunction of PGK may induce metabolic reprogramming and the Warburg effect. In this study, we demonstrated that PGK1, but not PGK2, may play a key role in tumorigenesis and is associated with metastasis. We observed an inverse correlation between PGK1 and the survival rate in several clinical cohorts through bioinformatics statistical and immunohistochemical staining analyses. Surprisingly, we found that PGK1 was significantly increased in adenocarcinoma compared with other subtypes. Thus, we established a PGK1-based proteomics dataset by a pull-down assay. We further investigated HIV-1 Tat Specific Factor 1 (HTATSF1), a potential binding partner, through protein–protein interactions. Then, we confirmed that PGK1 indeed bound to HTATSF1 by two-way immunoprecipitation experiments. In addition, we generated several mutant clones of PGK1 through site-directed mutagenesis, including mutagenesis of the N-terminal region, the enzyme catalytic domain, and the C-terminal region. We observed that even though the phosphoglycerate kinase activity had been inhibited, the migration ability induced by PGK1 was maintained. Moreover, our immunofluorescence staining also indicated the translocation of PGK1 from the cytoplasm to the nucleus and its colocalization with HTATSF1. From the results presented in this study, we propose a novel model in which the PGK1 binds to HTATSF1 and exerts functional control of cancer metastasis. In addition, we also showed a nonenzymatic function of PGK1. |
url |
https://doi.org/10.1038/s41420-021-00520-1 |
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