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Merck
CN
  • Positive regulation of PFKFB3 by PIM2 promotes glycolysis and paclitaxel resistance in breast cancer.

Positive regulation of PFKFB3 by PIM2 promotes glycolysis and paclitaxel resistance in breast cancer.

Clinical and translational medicine (2021-05-02)
Chao Lu, Pengyun Qiao, Yonghong Sun, Chune Ren, Zhenhai Yu
摘要

Breast 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. Mass 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. We 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. Our 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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Sigma-Aldrich
葡萄糖 (GO) 检测试剂盒, sufficient for 20 assays
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货号包装规格是否有货价格数量
60 mg
国内现货,预计发货时间 April 21, 2025
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CN¥1,096.69
Sigma-Aldrich
Anti-PIM2 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
登录查看公司和协议定价
货号包装规格是否有货价格数量
60 mg
国内现货,预计发货时间 April 21, 2025
详情...
CN¥1,096.69