ArticleWorld journal of gastroenterology2019
Signal transducer and activator of transcription 3 promotes the Warburg effect possibly by inducing pyruvate kinase M2 phosphorylation in liver precancerous lesions.
Article in World journal of gastroenterology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 32 citations in OpenAlex.
- Differential responses to folic acid in an established keloid fibroblast cell line are mediated by JAK1/2 and STAT3.PloS one · 2021Trial
- Signaling pathways and targeted interventions for precancers.Signal transduction and targeted therapy · 2026Review
- Coordinated gene expression within sustained STAT3-associated chromatin conformations contributes to hepatocellular carcinoma progression.Cancer communications (London, England) · 2025Article
- "Friends or foes": a new perspective of tumour metabolic transcriptional modification.Cell death & disease · 2025Review
- Hydrogen peroxide and cisplatin regulate the ROS/PKM2 pathway to affect the growth of cancer.American journal of cancer research · 2025Article
- Signaling pathways in liver cancer: pathogenesis and targeted therapy.Molecular biomedicine · 2024Review
- IL-6-Driven Autocrine Lactate Promotes Immune Escape of Uveal Melanoma.Investigative ophthalmology & visual science · 2024Article
- Review
- Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery.Journal of experimental & clinical cancer research : CR · 2024Review
- From immune equilibrium to tumor ecodynamics.Frontiers in oncology · 2024Article
- Oligonucleotide-Based Therapeutics for STAT3 Targeting in Cancer-Drug Carriers Matter.Cancers · 2023Review
- New Possible Ways to Use Exosomes in Diagnostics and Therapy via JAK/STAT Pathways.Pharmaceutics · 2023Review
- Review
- STAT proteins in cancer: orchestration of metabolism.Nature reviews. Cancer · 2023Review
- The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity.Open medicine (Warsaw, Poland) · 2023Article
- Role of Nrf2, STAT3, and Src as Molecular Targets for Cancer Chemoprevention.Pharmaceutics · 2022Review
- STAT3 pathway in cancers: Past, present, and future.MedComm · 2022Review
- Kangxianruangan granule‑containing serum mediated inhibition of hepatic oval cell differentiation into hepatocellular carcinoma cells via the Wnt‑1/β‑catenin signaling pathway.Molecular medicine reports · 2022Article
- The critical role of STAT3 in biogenesis of tumor-derived exosomes with potency of inducing cancer cachexia in vitro and in vivo.Oncogene · 2022Article
- A Case of Rapidly Progressing Hepatocellular Carcinoma after Administration of JAK Inhibitors to Treat Rheumatoid Arthritis.Case reports in rheumatology · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundStudy shows that signal transducer and activator of transcription 3 (STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 in myeloma. STAT3 and pyruvate kinase M2 (PKM2) can also be activated and enhance the Warburg effect in hepatocellular carcinoma. Precancerous lesions are critical to human and rodent hepatocarcinogenesis. However, the underlying molecular mechanism for the development of liver precancerous lesions remains unknown. We hypothesized that STAT3 promotes the Warburg effect possibly by upregulating p-PKM2 in liver precancerous lesions in rats.
aimTo investigate the mechanism of the Warburg effect in liver precancerous lesions in rats.
methodsA model of liver precancerous lesions was established by a modified Solt-Farber method. The liver pathological changes were observed by HE staining and immunohistochemistry. The transformation of WB-F344 cells induced with N-methyl-N'-nitro-N-nitrosoguanidine and hydrogen peroxide was evaluated by the soft agar assay and aneuploidy. The levels of glucose and lactate in the tissue and culture medium were detected with a spectrophotometer. The protein levels of glutathione S-transferase-π, proliferating cell nuclear antigen (PCNA), STAT3, and PKM2 were examined by Western blot and immunofluorescence.
resultsWe found that the Warburg effect was increased in liver precancerous lesions in rats. PKM2 and p-STAT3 were upregulated in activated oval cells in liver precancerous lesions in rats. The Warburg effect, p-PKM2, and p-STAT3 expression were also increased in transformed WB-F344 cells. STAT3 activation promoted the clonal formation rate, aneuploidy, alpha-fetoprotein expression, PCNA expression, G1/S phase transition, the Warburg effect, PKM2 phosphorylation, and nuclear translocation in transformed WB-F344 cells. Moreover, the Warburg effect was inhibited by stattic, a specific inhibitor of STAT3, and further reduced in transformed WB-F344 cells after the intervention for PKM2.
conclusionThe Warburg effect is initiated in liver precancerous lesions in rats. STAT3 activation promotes the Warburg effect by enhancing the phosphorylation of PKM2 in transformed WB-F344 cells.
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