ArticleBlood cancer discovery2023
HTLV-1 bZIP Factor-Induced Reprogramming of Lactate Metabolism and Epigenetic Status Promote Leukemic Cell Expansion.
Article in Blood cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Association BetweenPathogens (Basel, Switzerland) · 2025Pooled it
- Lactylation in influenza a virus infection: Current evidence, knowledge gaps, and future perspectives.Virulence · 2026Review
- FDXR upregulation by p63/p73 is a prognostic and therapeutic marker of adult T-cell leukemia/lymphoma.EMBO molecular medicine · 2026Article
- Virus infections and cancers: from mechanisms to therapeutics.Molecular biomedicine · 2026Review
- Repurposing Syrosingopine for Cancer Therapy: Lactate Trapping and ISR Sensitization as Metabolic Vulnerabilities.Oncology and therapy · 2026Review
- Lactate-associated transcriptomic alterations and malignant phenotypes in colorectal cancer.Discover oncology · 2026Article
- Viral-driven oncogenesis in T/NK-cell lymphomas: parallels and divergences between HTLV-1 and EBV.International journal of hematology · 2026Review
- Comprehensive single-cell metabolic profiling identifies targets to sensitize triple-negative breast cancer to chemo-immunotherapy.Cell reports. Medicine · 2026Article
- The bittersweet link between glucose metabolism, cellular microenvironment and viral infection.Virulence · 2025Review
- Viral oncogenesis in cancer: from mechanisms to therapeutics.Signal transduction and targeted therapy · 2025Review
- Molecular mechanisms of viral oncogenesis in haematological malignancies: perspectives from metabolic reprogramming, epigenetic regulation and immune microenvironment remodeling.Experimental hematology & oncology · 2025Review
- Epidemiology, molecular typing, microbiome-immune interactions and treatment strategies of endometrial cancer: a review.Frontiers in immunology · 2025Review
- Article
- ETS1 Function in Leukemia and Lymphoma.Advances in experimental medicine and biology · 2024Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acceleration of glycolysis is a common trait of cancer. A key metabolite, lactate, is typically secreted from cancer cells because its accumulation is toxic. Here, we report that a viral oncogene, HTLV-1 bZIP factor (HBZ), bimodally upregulates TAp73 to promote lactate excretion from adult T-cell leukemia-lymphoma (ATL) cells. HBZ protein binds to EZH2 and reduces its occupancy of the TAp73 promoter. Meanwhile, HBZ RNA activates TAp73 transcription via the BATF3-IRF4 machinery. TAp73 upregulates the lactate transporters MCT1 and MCT4. Inactivation of TAp73 leads to intracellular accumulation of lactate, inducing cell death in ATL cells. Furthermore, TAp73 knockout diminishes the development of inflammation in HBZ-transgenic mice. An MCT1/4 inhibitor, syrosingopine, decreases the growth of ATL cells in vitro and in vivo. MCT1/4 expression is positively correlated with TAp73 in many cancers, and MCT1/4 upregulation is associated with dismal prognosis. Activation of the TAp73-MCT1/4 pathway could be a common mechanism contributing to cancer metabolism. SIGNIFICANCE: An antisense gene encoded in HTLV-1, HBZ, reprograms lactate metabolism and epigenetic modification by inducing TAp73 in virus-positive leukemic cells. A positive correlation between TAp73 and its target genes is also observed in many other cancer cells, suggesting that this is a common mechanism for cellular oncogenesis. This article is featured in Selected Articles from This Issue, p. 337.
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Registered trials
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