ArticleClinical and translational medicine2021
Positive regulation of PFKFB3 by PIM2 promotes glycolysis and paclitaxel resistance in breast cancer.
Article in Clinical and translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 66 citations in OpenAlex.
- Multidimensional molecular mechanisms of drug resistance in breast cancer: Implications for clinical decision‑making and treatment strategies (Review).Oncology reports · 2026Review
- RNF34 restrains endometriosis through SREBP1-dependent metabolic-immune crosstalk.Cellular and molecular life sciences : CMLS · 2026Article
- P38γ drives aerobic glycolysis in liver sinusoidal endothelial cells and regulates alcoholic liver disease via the PFKFB3 signaling pathway.Molecular biology reports · 2026Article
- Txnip regulates glycolysis and tricarboxylic acid cycle balance to maintain bone homeostasis.Journal of orthopaedic translation · 2026Article
- PRMT6-mediated EZH2 arginine methylation is critical for breast cancer development.Oncogenesis · 2026Article
- Metabolic Vulnerabilities as a Therapeutic Target in Breast Cancer.Current oncology (Toronto, Ont.) · 2026Review
- Mechanistic role of glycolytic pathways in the tumor microenvironment in driving chemoresistance.Frontiers in cell and developmental biology · 2026Review
- The glycolytic enzyme PFKFB3 alleviates DNA damage and chondrocyte senescence in osteoarthritis.Cell death discovery · 2025Article
- PFKFB3 as a multifaceted driver and therapeutic target in castration-resistant prostate cancer.Cell death & disease · 2025Article
- Metabolic Reprogramming of Cancer Cells and Therapeutics Targeting Cancer Metabolism.Cancer medicine · 2025Review
- Lactate metabolism and lactylation in breast cancer: mechanisms and implications.Cancer metastasis reviews · 2025Review
- PYK2 promotes cell proliferation and epithelial-mesenchymal transition in endometriosis by phosphorylating Snail1.Molecular medicine (Cambridge, Mass.) · 2025Article
- Warburg effect and lactylation in cancer: mechanisms for chemoresistance.Molecular medicine (Cambridge, Mass.) · 2025Review
- Targeting macrophage polarization by inhibiting Pim2 alleviates inflammatory arthritis via metabolic reprogramming.Cellular & molecular immunology · 2025Article
- Repression of PFKFB3 sensitizes ovarian cancer to PARP inhibitors by impairing homologous recombination repair.Cell communication and signaling : CCS · 2025Article
- A novel glycolysis-related gene signature for predicting prognosis and immunotherapy efficacy in breast cancer.Frontiers in immunology · 2025Article
- PAK5-mediated PKM2 phosphorylation is critical for anaerobic glycolysis in endometriosis.Frontiers of medicine · 2024Article
- Phosphorylation of USP27X by PIM2 promotes glycolysis and breast cancer progression via deubiquitylation of MYC.Oncogene · 2024Article
- Article
- Arginine methylation of ALKBH5 by PRMT6 promotes breast tumorigenesis via LDHA-mediated glycolysis.Frontiers of medicine · 2024Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBreast cancer (BC) is one of the most common female malignancies in the world. Chemotherapeutic resistance is the major cause of BC therapy failure, leading to tumor recurrence and metastasis. Studies have illustrated the close relationship between glycolysis and BC progression and drug resistance. The key glycolysis regulator, PFKFB3 makes a difference during BC progression and drug resistance. However, the mechanism remains to be unknown.
methodsMass spectrometry analyses were used to found that PIM2 was a potential new binding protein of PFKFB3. Co-immunoprecipitated and western blot were used to verify the interaction between PIM2 and PFKFB3 in BC and the molecular mechanism by which PIM2 phosphorylates PFKFB3 in regulating the protein function. PFKFB3 mutant forms were used to demonstrate the need for PFKFB3 in BC drug resistance.
resultsWe identified that PIM2 is a new binding protein of PFKFB3. We used biochemical methods to determine that PIM2 can directly bind and change the phosphorylation of PFKFB3 at Ser478 to enhance PFKFB3 protein stability through the ubiquitin-proteasome pathway. Importantly, phosphorylation of PFKFB3 at Ser478 promoted glycolysis, BC cell growth, and paclitaxel resistance together with PIM2 in vitro and in vivo.
conclusionOur study demonstrates that PIM2 mediates PFKFB3 phosphorylation thus regulates glycolysis and paclitaxel resistance to promote tumor progression in BC and provides preclinical evidence for targeting PFKFB3 as a new strategy in BC treatment to battle paclitaxel resistance.
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