ALDOC and PGK1 coordinately induce glucose metabolism reprogramming and promote development of colorectal cancer
Abstract Colorectal cancer (CRC) remains a significant health challenge globally, demanding a comprehensive understanding of its molecular underpinnings for effective management. In this study, we investigated the role of Aldolase C (ALDOC), a glycolytic enzyme, in CRC pathogenesis. Transcriptomic a...
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2025-06-01
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| Online Access: | https://doi.org/10.1186/s10020-025-01252-z |
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| author | Liyong Huang Yixin Tong Xu Li Wei Wang Zhen Wang Bingchen Chen Jifu E. Ruzhen Zhou Hantao Wang Jinghu He |
| author_facet | Liyong Huang Yixin Tong Xu Li Wei Wang Zhen Wang Bingchen Chen Jifu E. Ruzhen Zhou Hantao Wang Jinghu He |
| author_sort | Liyong Huang |
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| description | Abstract Colorectal cancer (CRC) remains a significant health challenge globally, demanding a comprehensive understanding of its molecular underpinnings for effective management. In this study, we investigated the role of Aldolase C (ALDOC), a glycolytic enzyme, in CRC pathogenesis. Transcriptomic analysis of CRC tissues from The Cancer Genome Atlas (TCGA) revealed a substantial upregulation of ALDOC, correlating with adverse clinical outcomes. Immunohistochemical (IHC) staining of locally collected patient-derived tissues corroborated these findings, demonstrating elevated ALDOC expression in tumor tissues, particularly in advanced stages. Functional studies elucidated the regulatory role of ALDOC in CRC cell phenotypes. ALDOC knockdown significantly inhibited cell proliferation, induced apoptosis, arrested cell cycle progression, and suppressed cell migration in vitro. Moreover, in vivo studies using xenograft models confirmed that ALDOC knockdown attenuated tumor growth. Mechanistically, ALDOC was found to interact with hypoxia-inducible factor 1 alpha (HIF1A) and enhance its transcriptional activity on phosphoglycerate kinase 1 (PGK1), a key glycolytic enzyme. Dual-luciferase reporter assays and chromatin immunoprecipitation experiments validated the ALDOC-mediated transcriptional activation of PGK1. Further functional rescue experiments revealed a synergistic interplay between ALDOC and PGK1 in regulating CRC cell phenotypes. Additionally, ALDOC was implicated in promoting aerobic glycolysis in CRC cells, potentially through PGK1 regulation. Collectively, our findings unveil ALDOC as a critical regulator of CRC pathogenesis, offering insights into its potential as a therapeutic target and highlighting the ALDOC/PGK1 axis as a promising avenue for further investigation in CRC. |
| format | Article |
| id | doaj-art-ac8f2cc7089a4aa59e1878ea6d594640 |
| institution | OA Journals |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
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| series | Molecular Medicine |
| spelling | doaj-art-ac8f2cc7089a4aa59e1878ea6d5946402025-08-20T02:36:50ZengBMCMolecular Medicine1528-36582025-06-0131111410.1186/s10020-025-01252-zALDOC and PGK1 coordinately induce glucose metabolism reprogramming and promote development of colorectal cancerLiyong Huang0Yixin Tong1Xu Li2Wei Wang3Zhen Wang4Bingchen Chen5Jifu E.6Ruzhen Zhou7Hantao Wang8Jinghu He9Department of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of GI Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Colorectal Surgery, The First Affiliated Hospital of Naval Medical UniversityDepartment of Colorectal Surgery, The First Affiliated Hospital of Naval Medical UniversityDepartment of Colorectal Surgery, The First Affiliated Hospital of Naval Medical UniversityDepartment of Colorectal Surgery, The First Affiliated Hospital of Naval Medical UniversityDepartment of Colorectal Surgery, The First Affiliated Hospital of Naval Medical UniversityDepartment of Colorectal Surgery, The First Affiliated Hospital of Naval Medical UniversityDepartment of Colorectal Surgery, The First Affiliated Hospital of Naval Medical UniversityDepartment of General Surgery, Shanghai 411 Hospital, RongTong Medical Healthcare Group Co. Ltd.Abstract Colorectal cancer (CRC) remains a significant health challenge globally, demanding a comprehensive understanding of its molecular underpinnings for effective management. In this study, we investigated the role of Aldolase C (ALDOC), a glycolytic enzyme, in CRC pathogenesis. Transcriptomic analysis of CRC tissues from The Cancer Genome Atlas (TCGA) revealed a substantial upregulation of ALDOC, correlating with adverse clinical outcomes. Immunohistochemical (IHC) staining of locally collected patient-derived tissues corroborated these findings, demonstrating elevated ALDOC expression in tumor tissues, particularly in advanced stages. Functional studies elucidated the regulatory role of ALDOC in CRC cell phenotypes. ALDOC knockdown significantly inhibited cell proliferation, induced apoptosis, arrested cell cycle progression, and suppressed cell migration in vitro. Moreover, in vivo studies using xenograft models confirmed that ALDOC knockdown attenuated tumor growth. Mechanistically, ALDOC was found to interact with hypoxia-inducible factor 1 alpha (HIF1A) and enhance its transcriptional activity on phosphoglycerate kinase 1 (PGK1), a key glycolytic enzyme. Dual-luciferase reporter assays and chromatin immunoprecipitation experiments validated the ALDOC-mediated transcriptional activation of PGK1. Further functional rescue experiments revealed a synergistic interplay between ALDOC and PGK1 in regulating CRC cell phenotypes. Additionally, ALDOC was implicated in promoting aerobic glycolysis in CRC cells, potentially through PGK1 regulation. Collectively, our findings unveil ALDOC as a critical regulator of CRC pathogenesis, offering insights into its potential as a therapeutic target and highlighting the ALDOC/PGK1 axis as a promising avenue for further investigation in CRC.https://doi.org/10.1186/s10020-025-01252-zColorectal cancerALDOCPGK1GlycolysisMolecular mechanism |
| spellingShingle | Liyong Huang Yixin Tong Xu Li Wei Wang Zhen Wang Bingchen Chen Jifu E. Ruzhen Zhou Hantao Wang Jinghu He ALDOC and PGK1 coordinately induce glucose metabolism reprogramming and promote development of colorectal cancer Molecular Medicine Colorectal cancer ALDOC PGK1 Glycolysis Molecular mechanism |
| title | ALDOC and PGK1 coordinately induce glucose metabolism reprogramming and promote development of colorectal cancer |
| title_full | ALDOC and PGK1 coordinately induce glucose metabolism reprogramming and promote development of colorectal cancer |
| title_fullStr | ALDOC and PGK1 coordinately induce glucose metabolism reprogramming and promote development of colorectal cancer |
| title_full_unstemmed | ALDOC and PGK1 coordinately induce glucose metabolism reprogramming and promote development of colorectal cancer |
| title_short | ALDOC and PGK1 coordinately induce glucose metabolism reprogramming and promote development of colorectal cancer |
| title_sort | aldoc and pgk1 coordinately induce glucose metabolism reprogramming and promote development of colorectal cancer |
| topic | Colorectal cancer ALDOC PGK1 Glycolysis Molecular mechanism |
| url | https://doi.org/10.1186/s10020-025-01252-z |
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