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PGAM1 regulation of ASS1 contributes to the progression of breast cancer through the cAMP/AMPK/CEBPB pathway
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PGAM1 regulation of ASS1 contributes to the progression of breast cancer through the cAMP/AMPK/CEBPB pathway
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Journal Article
PGAM1 regulation of ASS1 contributes to the progression of breast cancer through the cAMP/AMPK/CEBPB pathway
2022
Overview
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. Knockdown of phosphoglycerate mutase 1 (PGAM1) could reconstruct the expression of ASS1 in breast cancer (BC) cells, resulting in a decrease in tumor growth and exerting antitumor effects via cAMP/AMPK/CEBPB axis. These findings constructed a new theoretical background for PGAM1‐mediated tumor progression, and the elements in this molecular network could be the target of BC treatment.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
Subject
/ AMP-Activated Protein Kinases
/ AMPK
/ Argininosuccinate Synthase - metabolism
/ ASS1
/ CCAAT-Enhancer-Binding Protein-beta
/ CEBPB
/ Cell Proliferation - genetics
/ Enzymes
/ Female
/ Humans
/ Hypoxia
/ Kinases
/ Patients
/ PGAM1
/ Phosphoglycerate Mutase - genetics
/ Phosphoglycerate Mutase - metabolism
/ Proteins
/ Reagents
/ Tumors
