Metabolic protein phosphoglycerate kinase 1 confers lung cancer migration by directly binding HIV Tat specific factor 1

Yu Chan Chang, Ming Hsien Chan, Chien Hsiu Li, Chih Jen Yang, Yu Wen Tseng, Hsing Fang Tsai, Jean Chiou*, Michael Hsiao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish
Article number135
JournalCell Death Discovery
Volume7
Issue number1
DOIs
StatePublished - Jun 2021

Fingerprint

Dive into the research topics of 'Metabolic protein phosphoglycerate kinase 1 confers lung cancer migration by directly binding HIV Tat specific factor 1'. Together they form a unique fingerprint.

Cite this