PGAM1: a potential therapeutic target mediating Wnt/β-catenin signaling drives breast cancer progression

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 P...

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Main Authors: Yongxuan Wang, Wei Liu, Xudong Lai, Haixiong Miao, Xifeng Xiong
Format: Article
Language:English
Published: Springer 2025-02-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-01939-z
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author Yongxuan Wang
Wei Liu
Xudong Lai
Haixiong Miao
Xifeng Xiong
author_facet Yongxuan Wang
Wei Liu
Xudong Lai
Haixiong Miao
Xifeng Xiong
author_sort Yongxuan Wang
collection DOAJ
description 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.
format Article
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institution DOAJ
issn 2730-6011
language English
publishDate 2025-02-01
publisher Springer
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series Discover Oncology
spelling doaj-art-f44bdc4ff7dd44d0b9efd41e36a62b522025-08-20T02:43:13ZengSpringerDiscover Oncology2730-60112025-02-0116111710.1007/s12672-025-01939-zPGAM1: a potential therapeutic target mediating Wnt/β-catenin signaling drives breast cancer progressionYongxuan Wang0Wei Liu1Xudong Lai2Haixiong Miao3Xifeng Xiong4Department of Pathology, Guangzhou Red Cross Hospital of Jinan UniversityDepartment of Breast Surgery, Guangzhou Red Cross Hospital of Jinan UniversityDepartment of Infectious Disease, Guangzhou Red Cross Hospital of Jinan UniversityDepartment of Orthopedics, Guangzhou Red Cross Hospital of Jinan UniversityGuangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital of Jinan UniversityAbstract 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.https://doi.org/10.1007/s12672-025-01939-zPGAM1Breast cancerWnt/β-catenin signalingCell proliferationCell migration
spellingShingle Yongxuan Wang
Wei Liu
Xudong Lai
Haixiong Miao
Xifeng Xiong
PGAM1: a potential therapeutic target mediating Wnt/β-catenin signaling drives breast cancer progression
Discover Oncology
PGAM1
Breast cancer
Wnt/β-catenin signaling
Cell proliferation
Cell migration
title PGAM1: a potential therapeutic target mediating Wnt/β-catenin signaling drives breast cancer progression
title_full PGAM1: a potential therapeutic target mediating Wnt/β-catenin signaling drives breast cancer progression
title_fullStr PGAM1: a potential therapeutic target mediating Wnt/β-catenin signaling drives breast cancer progression
title_full_unstemmed PGAM1: a potential therapeutic target mediating Wnt/β-catenin signaling drives breast cancer progression
title_short PGAM1: a potential therapeutic target mediating Wnt/β-catenin signaling drives breast cancer progression
title_sort pgam1 a potential therapeutic target mediating wnt β catenin signaling drives breast cancer progression
topic PGAM1
Breast cancer
Wnt/β-catenin signaling
Cell proliferation
Cell migration
url https://doi.org/10.1007/s12672-025-01939-z
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