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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
PGAM1: a potential therapeutic target mediating Wnt/β-catenin signaling drives breast cancer progression
Yongxuan Wang1, Wei Liu2, Xudong Lai3
1Department of Pathology, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, 510220, Guangdong, China.
Abstract:
Phosphoglycerate mutase 1 (PGAM1) has been identified as a key player in the progression and metastasis of various human cancer types, including breast cancer (BC); however, its precise oncogenic mechanism remains unclear. The present study aimed to investigate the oncogenic mechanisms of PGAM1 and establish its potential as a therapeutic target. Comprehensive analyses from the Tumor Immune Estimation Resource 2.0 and The Cancer Genome Atlas databases revealed a significant upregulation of PGAM1 in BC, correlating with poor clinical outcomes. Additionally, elevated expression of PGAM1 was confirmed in clinical BC samples. Silencing PGAM1 with specific small hairpin RNA in BC cells resulted in a marked reduction in cell proliferation, invasiveness and migration, alongside increased apoptosis and cell cycle arrest. In vivo experiments using tumor-bearing nude mice demonstrated that PGAM1 knockdown significantly reduced tumor volume and weight, effectively inhibiting tumor growth. Mechanistic investigations suggested that PGAM1 promoted BC tumorigenesis through the activation of the Wnt/β-catenin signaling pathway, both in vitro and in vivo. Therefore, the upregulation of PGAM1 in BC enhances malignancy via the Wnt/β-catenin signaling pathway, highlighting PGAM1 as a promising therapeutic target for BC treatment.
Insights
Phosphoglycerate mutase 1 (PGAM1) drives breast cancer (BC) growth and spread by activating the Wnt/β-catenin pathway. Targeting PGAM1 offers a promising therapeutic strategy for BC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Phosphoglycerate mutase 1 (PGAM1) is implicated in various cancers, but its role in breast cancer (BC) pathogenesis is not fully understood.
- Understanding PGAM1's oncogenic mechanisms is crucial for developing effective BC therapies.
Purpose of the Study:
- To elucidate the oncogenic mechanisms of PGAM1 in breast cancer.
- To evaluate PGAM1 as a potential therapeutic target for BC.
Main Methods:
- Bioinformatic analysis using TCGA and Tumor Immune Estimation Resource 2.0 databases.
- In vitro studies involving PGAM1 knockdown in BC cell lines using shRNA.
- In vivo tumor xenograft models in nude mice.
- Western blot analysis to investigate signaling pathways.
Main Results:
- PGAM1 was significantly upregulated in BC tissues and correlated with poor clinical outcomes.
- PGAM1 knockdown reduced BC cell proliferation, invasion, migration, and induced apoptosis and cell cycle arrest.
- PGAM1 inhibition suppressed tumor growth in vivo.
- PGAM1 promotes BC tumorigenesis via activation of the Wnt/β-catenin signaling pathway.
Conclusions:
- Upregulated PGAM1 enhances BC malignancy through the Wnt/β-catenin pathway.
- PGAM1 is a potential therapeutic target for breast cancer treatment.
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