ArticleCellular and molecular gastroenterology and hepatology2023
PFKFB4 Drives the Oncogenicity in TP53-Mutated Hepatocellular Carcinoma in a Phosphatase-Dependent Manner.
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 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- The regulatory roles of non-coding RNAs in aerobic glycolysis and therapeutic potential in pancreatic ductal adenocarcinoma.Annals of medicine · 2026Review
- PFKFB4 promotes M2 polarization of tumor-associated macrophages through aerobic glycolysis-mediated modification of histone H3K18 lactylation in hepatocellular carcinoma.Cancer & metabolism · 2026Article
- Metabolic Vulnerabilities as a Therapeutic Target in Breast Cancer.Current oncology (Toronto, Ont.) · 2026Review
- Proteomic Identification of PFKFB3 and PFKFB4 Associated with Coenzyme Metabolism and Redox Imbalance in Dairy Cows with Clinical Mastitis.Antioxidants (Basel, Switzerland) · 2026Article
- Metabolic reprogramming-driven resistance to multi-kinase inhibitors in hepatocellular carcinoma: molecular mechanisms and therapeutic opportunities.Molecular cancer · 2026Review
- Fibrillarin and fibrillarin-like their role in cancer progression: new approaches and perspectives.Molecular biology reports · 2026Review
- Identification and validation of prognostic genes related to glycolysis and M2 macrophage in hepatocellular carcinoma: an integrated analysis of bulk RNA sequencing and single-cell RNA sequencing.Frontiers in immunology · 2026Article
- Evaluation of therapeutic efficacy in hepatocellular carcinoma ablation based on CT radiomics and deep learning multimodal models.Frontiers in oncology · 2026Article
- Mitochondrial energy metabolism genes as prognostic biomarkers in clear cell renal cell carcinoma via single-cell and bulk RNA sequencing analyses.Discover oncology · 2025Article
- Targeting phosphofructokinase 2 the isoform PFKFB4 suppresses glioblastoma proliferation and malignancy.Genes & genomics · 2025Article
- Non-canonical splice variant of PFKFB4 in hepatocellular carcinoma activates AKT through direct interaction.JHEP reports : innovation in hepatology · 2025Article
- Roles of Hypoxia and Mitochondrial Energy Metabolism Related Genes in Predicting the Prognosis of Liver Hepatocellular Carcinoma.Digestive diseases and sciences · 2025Article
- Identifying genes associated with Sorafenib resistance in hepatocellular carcinoma to develop risk model.Discover oncology · 2025Article
- Identification and validation of a lenvatinib resistance-related prognostic signature in HCC, in which PFKFB4 contributes to tumor progression and lenvatinib resistance.BMC gastroenterology · 2025Article
- The Pentose Phosphate Pathway: From Mechanisms to Implications for Gastrointestinal Cancers.International journal of molecular sciences · 2025Review
- Metabolic reprogramming of glucose: the metabolic basis for the occurrence and development of hepatocellular carcinoma.Frontiers in oncology · 2025Review
- Development and Validation of a Carbohydrate Metabolism-Related Model for Predicting Prognosis and Immune Landscape in Hepatocellular Carcinoma Patients.Current medical science · 2024Article
- Metabolomic biomarkers in liquid biopsy: accurate cancer diagnosis and prognosis monitoring.Frontiers in oncology · 2024Review
- Reciprocal interactions between malignant cells and macrophages enhance cancer stemness and M2 polarization in HBV-associated hepatocellular carcinoma.Theranostics · 2024Article
- PFKFB4 Is a Metabolic Driver of HCC Progression and Chemoresistance Through ROS Mitigation.Cellular and molecular gastroenterology and hepatology · 2023Article
Corrections and comments
- Commented on by
Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsMetabolic reprogramming is recognized as a cancer hallmark intimately linked to tumor hypoxia, which supports rapid tumor growth and mitigates the consequential oxidative stress. Phosphofructokinase-fructose bisphosphatase (PFKFB) is a family of bidirectional glycolytic enzymes possessing both kinase and phosphatase functions and has emerged as important oncogene in multiple types of cancer. However, its clinical relevance, functional significance, and underlying mechanistic insights in hepatocellular carcinoma (HCC), the primary malignancy that develops in the most important metabolic organ, has never been addressed.
methodsPFKFB4 expression was examined by RNA sequencing in The Cancer Genome Atlas and our in-house HCC cohort. The up-regulation of PFKFB4 expression was confirmed further by quantitative polymerase chain reaction in an expanded hepatitis B virus-associated HCC cohort followed by clinicopathologic correlation analysis. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated PFKFB4 knockout cells were generated for functional characterization in vivo, targeted metabolomic profiling, as well as RNA sequencing analysis to comprehensively examine the impact of PFKFB4 loss in HCC.
resultsPFKFB4 expression was up-regulated significantly in HCC and correlated positively with TP53 and TSC2 loss-of-function mutations. In silico transcriptome-based analysis further revealed PFKFB4 functions as a critical hypoxia-inducible gene. Clinically, PFKFB4 up-regulation was associated with more aggressive tumor behavior. Functionally, CRISPR/Cas9-mediated PFKFB4 knockout significantly impaired in vivo HCC development. Targeted metabolomic profiling revealed that PFKFB4 functions as a phosphatase in HCC and its ablation caused an accumulation of metabolites in downstream glycolysis and the pentose phosphate pathway. In addition, PFKFB4 loss induced hypoxia-responsive genes in glycolysis and reactive oxygen species detoxification. Conversely, ectopic PFKFB4 expression conferred sorafenib resistance.
conclusionsPFKFB4 up-regulation supports HCC development and shows therapeutic implications.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.