ArticleCancer & metabolism2024
PAF1/HIF1α axis rewires the glycolytic metabolism to fuel aggressiveness of pancreatic cancer.
Article in Cancer & metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Lactate-induced epithelial-mesenchymal transition: a metabolic nexus in pancreatic cancer metastasis.Translational cancer research · 2026Review
- Targeting the Warburg Effect in Anaplastic Thyroid Carcinoma: Metabolic Vulnerabilities and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Intermittent fasting synergizes with GCN5 inhibition to suppress RBM5-AS1/GCN5/PGC-1α-driven Warburg metabolism in ovarian cancer.Functional & integrative genomics · 2026Article
- USP4 promotes non-small cell lung cancer tumorigenesis by antagonizing CNOT4-mediated degradation of PAF1.Respiratory research · 2026Article
- Experience-mediated transcriptional memory correlates with hypoxia resistance in the nervous system of the sea hareAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2025Article
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Authors and funding
9 authors.
Funding
Abstract
backgroundPAF1/PD2 deregulation contributes to tumorigenesis, drug resistance, and cancer stem cell maintenance in Pancreatic Cancer (PC). Recent studies demonstrate that metabolic reprogramming plays a role in PC progression, but the mechanism is poorly understood. Here, we focused on examining the role of PAF1/PD2 in the metabolic rewiring of PC.
methodsCell lines were transfected with shRNAs to knockdown PAF1/PD2. Metabolic genes regulated by PAF1/PD2 were identified by qPCR/western blot, and metabolic assays were performed. Immunoprecipitations/ChIP were performed to identify PAF1/PD2 protein partners and confirm PAF1/HIF1α sub-complex binding to LDHA.
resultsPAF1 and LDHA showed progressively increased expression in human pancreatic tumor sections. Aerobic glycolysis genes were downregulated in PAF1-depleted PC cells. Metabolic assays indicated a decreased lactate production and glucose uptake in knockdown cells. Furthermore, PAF1/PD2 depletion showed a reduced glycolytic rate and increased oxidative phosphorylation by ECAR and OCR analysis. Interestingly, we identified that HIF1α interacts and co-localizes with PAF1, specifically in PC cells. We also observed that the PAF1/PD2-HIF1α complex binds to the LDHA promoter to regulate its expression, reprogramming the metabolism to utilize the aerobic glycolysis pathway preferentially.
conclusionOverall, the results indicate that PAF1/PD2 rewires PC metabolism by interacting with HIF1α to regulate the expression of LDHA.
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