PGAM1 regulation of ASS1 contributes to the progression of breast cancer through the cAMP/AMPK/CEBPB pathway

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.

Novel genome-wide DNA methylation profiling reveals distinct epigenetic landscape, prognostic model and cellular composition of early-stage lung adenocarcinoma

“…The PI3K-Akt signaling pathway regulates tumor cell proliferation and inhibits apoptosis [ 47 – 49 ] in various types of tumors, and is associated with lung cancer lymph node micrometastasis [ 50 ]. Similarly, cAMP, as a second messenger in the body, directly regulates cell metabolism, growth, and apoptosis, thereby promoting tumor progression [ 51 , 52 ]. Additionally, while cell adhesion molecules are often linked to tumor metastasis, it is possible that cancer cells have already begun to disseminate or even micro-metastasize in the early stages, as observed in early breast cancer patients with metastatic tumor cells in the bone marrow [ 53 , 54 ].…”

Baicalein Attenuates Myocardial Fibrosis via Directly Targeting Phosphoglycerate Mutase 1

“…Phosphoglycerate mutase 1 (PGAM1) is a crucial glycolytic enzyme, and its expression status has been confirmed to be associated with tumor progression and metastasis [22]. Previous study has demonstrated target PGAM1 could inhibit the cell migration [8].…”

Significance of liquid-liquid phase separation (LLPS)-related genes in breast cancer: a multi-omics analysis

“…In cancer biology, PGAM1 has garnered attention due to its association with tumorigenesis, tumor progression, and therapeutic resistance [ 44 ]. Several studies have demonstrated that PGAM1 is frequently upregulated in various types of cancers, including lung, breast, colorectal, and liver cancers [ 45 , 46 ]. Elevated expression of PGAM1 is often correlated with aggressive tumor phenotypes, poor prognosis, and reduced patient survival rates [ 46 ].…”

“…Several studies have demonstrated that PGAM1 is frequently upregulated in various types of cancers, including lung, breast, colorectal, and liver cancers [ 45 , 46 ]. Elevated expression of PGAM1 is often correlated with aggressive tumor phenotypes, poor prognosis, and reduced patient survival rates [ 46 ].…”

“…It exerts its oncogenic effects by influencing key signaling pathways involved in cell cycle progression, such as the AKT/mTOR pathway and the MAPK pathway [ 45 ]. Additionally, PGAM1 enhances the resistance of cancer cells to oxidative stress and apoptosis, enabling their survival and contributing to chemoresistance [ 46 ].…”