ArticleCellular and molecular gastroenterology and hepatology2023
ZEB1 Transcriptionally Activates PHGDH to Facilitate Carcinogenesis and Progression of HCC.
Article in Cellular and molecular gastroenterology and hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Role of epithelial-mesenchymal transition (EMT) in malignancies: current status and future prospects.Signal transduction and targeted therapy · 2026Review
- PHGDH Orchestrates Cell Cycle Progression to Drive Cardiomyocyte Proliferation and Myocardial Regeneration via TGF-β/Smad Signalling Pathway.Cell proliferation · 2026Article
- Zinc finger proteins (ZFPs) in health and disease.Molecular biomedicine · 2026Review
- Decoding amino acid metabolism in hepatocellular carcinoma: critical nodes and novel therapeutic strategy.Frontiers in oncology · 2026Review
- The "serine code" of metabolic reprogramming: multidimensional roles of the serine synthesis pathway in tumors and novel breakthroughs for targeted therapy.Frontiers in immunology · 2026Review
- Epithelial to Mesenchymal Transition Transcriptional Regulator ZEB1 in Liver Cancer: Oncogenic Roles and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Serine metabolism reprogramming in cancer: a multi-tiered regulatory framework.Acta biochimica et biophysica Sinica · 2025Review
- ZEB1 stratifies the response to Sorafenib and Mdivi-1 combination therapy in hepatocellular carcinoma.Scientific reports · 2025Article
- Long non-coding RNA MINCR silencing contributes to suppressed gemcitabine resistance in bladder cancer by blocking the ZEB1/PHGDH axis through microRNA-876-5p up-regulation.Journal of molecular histology · 2025Article
- Serine metabolism in tumor progression and immunotherapy.Discover oncology · 2025Review
- Interactions between the metabolic reprogramming of liver cancer and tumor microenvironment.Frontiers in immunology · 2025Review
- Spatial transcriptomics reveals unique metabolic profile and key oncogenic regulators of cervical squamous cell carcinoma.Journal of translational medicine · 2024Article
- A positive feedback loop of SRSF9/USP22/ZEB1 promotes the progression of ovarian cancer.Cancer biology & therapy · 2024Article
- Non-canonical function of PHGDH promotes HCC metastasis by interacting with METTL3.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Loss of USP10 promotes hepatocellular carcinoma proliferation by regulating the serine synthesis pathway through inhibition of LKB1 activity.Cancer science · 2024Article
- Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives.Signal transduction and targeted therapy · 2024Review
- PHGDH: a novel therapeutic target in cancer.Experimental & molecular medicine · 2024Review
- Identifying Proteins and Amino Acids Associated with Liver Cancer Risk: A Study Utilizing Mendelian Randomization and Bulk RNA Sequencing Analysis.Journal of personalized medicine · 2024Article
- ZEB1 Fuels Serine Metabolism to Promote HCC Metastasis.Cellular and molecular gastroenterology and hepatology · 2023Article
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsPhosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme of the de novo serine synthesis pathway (SSP), has been implicated in the carcinogenesis and metastasis of hepatocellular carcinoma (HCC) because of its excessive expression and promotion of SSP. In previous experiments we found that SSP flux was diminished by knockdown of zinc finger E-box binding homeobox 1 (ZEB1), a stimulator of HCC metastasis, but the underlying mechanism remains largely unknown. Here, we aimed to determine how SSP flux is regulated by ZEB1 and the contribution of such regulation to carcinogenesis and progression of HCC.
methodsWe used genetic mice with Zeb1 knockout in liver specifically to determine whether Zeb1 deficiency impacts HCC induced by the carcinogen diethylnitrosamine plus CCl
resultsWe identified that ZEB1 activates PHGDH transcription by binding to a nonclassic binding site within its promoter region. Up-regulated PHGDH augments SSP flux to enable HCC cells to be more invasive, proliferative, and resistant to reactive oxygen species and sorafenib. Orthotopic xenograft and bioluminescence assays have shown that ZEB1 deficiency significantly impairs the tumorigenesis and metastasis of HCC, and such impairments can be rescued to a large extent by exogenous expression of PHGDH. These results were confirmed by the observation that conditional knockout of ZEB1 in mouse liver dramatically impedes carcinogenesis and progression of HCC induced by diethylnitrosamine/CCl
conclusionsZEB1 plays a crucial role in stimulating carcinogenesis and progression of HCC by activating PHGDH transcription and subsequent SSP flux, deepening our knowledge of ZEB1 as a transcriptional factor in fostering the development of HCC via reprogramming the metabolic pathway.
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