ArticleAmerican journal of cancer research2021
Necroptosis pathway blockage attenuates PFKFB3 inhibitor-induced cell viability loss and genome instability in colorectal cancer cells.
Article in American journal of cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- SUN5 interacts with TRIM28, enhancing IκBα ubiquitination to promote glycolysis in colorectal cancer cells.Acta biochimica et biophysica Sinica · 2025Article
- Chaperonin-containing tailless complex polypeptide 1 subunit 6A negatively regulates autophagy and protects colorectal cancer cells from cisplatin-induced cytotoxicity.World journal of gastroenterology · 2025Article
- Impact of glycolysis enzymes and metabolites in regulating DNA damage repair in tumorigenesis and therapy.Cell communication and signaling : CCS · 2025Review
- Role of glucose metabolic reprogramming in colorectal cancer progression and drug resistance.Translational oncology · 2024Review
- Tumor Vessel Normalization via PFKFB3 Inhibition Alleviates Hypoxia and Increases Tumor Necrosis in Rectal Cancer upon Radiotherapy.Cancer research communications · 2024Article
- PFKFB3 deprivation attenuates the cisplatin resistance via blocking its autophagic elimination in colorectal cancer cells.Frontiers in pharmacology · 2024Article
- Ferroptosis, Necroptosis, and Pyroptosis in Gastrointestinal Cancers: The Chief Culprits of Tumor Progression and Drug Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Glycolysis: an emerging regulator of osteoarthritis.Frontiers in immunology · 2023Review
- Necroptosis pathways in tumorigenesis.Seminars in cancer biology · 2022Review
- The role of PFKFB3 in maintaining colorectal cancer cell proliferation and stemness.Molecular biology reports · 2022Review
- Identification and validation of necroptosis-related prognostic gene signature and tumor immune microenvironment infiltration characterization in esophageal carcinoma.BMC gastroenterology · 2022Article
- Necroptosis Identifies Novel Molecular Phenotypes and Influences Tumor Immune Microenvironment of Lung Adenocarcinoma.Frontiers in immunology · 2022Article
- Glucose metabolism inhibitor PFK-015 combined with immune checkpoint inhibitor is an effective treatment regimen in cancer.Oncoimmunology · 2022Article
- The significance of glycolysis in tumor progression and its relationship with the tumor microenvironment.Frontiers in pharmacology · 2022Review
- Prognosis analysis of necroptosis-related genes in colorectal cancer based on bioinformatic analysis.Frontiers in genetics · 2022Article
- The role of necroptosis in disease and treatment.MedComm · 2021Review
- AICAR enhances the cytotoxicity of PFKFB3 inhibitor in an AMPK signaling-independent manner in colorectal cancer cells.Medical oncology (Northwood, London, England) · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells prone to utilize aerobic glycolysis other than oxidative phosphorylation to sustain its continuous cell activity in the stress microenvironment. Meanwhile, cancer cells generally suffer from genome instability, and both radiotherapy and chemotherapy may arouse DNA strand break, a common phenotype of genome instability. Glycolytic enzyme PFKFB3 (6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3), plays essential roles in variety physiology and pathology processes, and generally maintain high level in cancer cells. Although this protein has been reported to involve in genome instability, its role remains unclear and controversial. Here, we showed that PFK-15, a PFKFB3 inhibitor, obviously induced apoptosis, cell viability loss, and inhibited cell proliferation/migration. Besides, PFK-15 was also found to induce necroptosis, as it not only up-regulated the phosphorylated RIP1, RIP3 and MLKL, but also enhanced the interaction between RIP3 and RIP1/MLKL, all of which are characterization of necroptosis induction. Both genetically and pharmacologically deprivation of necroptosis attenuated the cytotoxic effect of PFK-15. Besides, PFK-15 increased the γ-H2AX level and micronuclei formation, markers for genome instability, and inhibition of necroptosis attenuated these phenotypes. Collectively, the presented data demonstrated that PFK-15 induced genome instability and necroptosis, and deprivation of necroptosis attenuated cytotoxicity and genotoxicity of PFK-15 in colorectal cancer cells, thereby revealing a more intimate relationship among PFKFB3, necroptosis and genome instability.
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34094669PMC8167677W3172024719What OpenQuestion holds
Registered trials
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