Abstract |
Phosphoglycerate mutase 1 (PGAM1) is a crucial glycolytic enzyme, and its expression status has been confirmed to be associated with tumor progression and metastasis. However, the precise role and other biological functions of PGAM1 remain unclear. Here, we report that PGAM1 expression is upregulated and related to poor prognosis in patients with breast cancer (BC). Functional experiments showed that knockdown of PGAM1 could suppress the proliferation, invasion, migration, and epithelial-mesenchymal transition of BC cells. Through RNA sequencing, we found that argininosuccinate synthase 1 (ASS1) expression was markedly upregulated in BC cells following PGAM1 knockdown, and it is required to suppress the malignant biological behavior of BC cells. Importantly, we demonstrated that PGAM1 negatively regulates ASS1 expression through the cAMP/AMPK/CEBPB axis. In vivo experiments further validated that PGAM1 promoted tumor growth in BC by altering ASS1 expression. Finally, immunohistochemical analysis showed that downregulated ASS1 levels were associated with PGAM1 expression and poor prognosis in patients with BC. Our study provides new insight into the regulatory mechanism of PGAM1-mediated BC progression that might shed new light on potential targets and combination therapeutic strategies for BC treatment.
|
Authors | Min Liu, Runmei Li, Min Wang, Ting Liu, Qiuru Zhou, Dong Zhang, Jian Wang, Meng Shen, Xiubao Ren, Qian Sun |
Journal | Molecular oncology
(Mol Oncol)
Vol. 16
Issue 15
Pg. 2843-2860
(08 2022)
ISSN: 1878-0261 [Electronic] United States |
PMID | 35674458
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | © 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. |
Chemical References |
- CCAAT-Enhancer-Binding Protein-beta
- CEBPB protein, human
- AMP-Activated Protein Kinases
- Phosphoglycerate Mutase
- phosphoglycerate mutase 1, human
- Argininosuccinate Synthase
|
Topics |
- AMP-Activated Protein Kinases
- Argininosuccinate Synthase
(metabolism)
- Breast Neoplasms
(genetics)
- CCAAT-Enhancer-Binding Protein-beta
- Cell Line, Tumor
- Cell Proliferation
(genetics)
- Female
- Humans
- Phosphoglycerate Mutase
(genetics, metabolism)
|