ZFP64 drives glycolysis-mediated stem cell-like properties and tumorigenesis in breast cancer
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View abstract on PubMed
Summary
This summary is machine-generated.Zinc Finger Protein 64 (ZFP64) promotes breast cancer (BC) stem cell properties and tumor growth by activating glycolysis. Targeting ZFP64 and the glycolytic pathway may offer new therapeutic strategies for aggressive BC.
Area Of Science
- Oncology
- Molecular Biology
- Biochemistry
Background
- Breast cancer (BC) presents a significant clinical challenge due to its aggressiveness and poor prognosis.
- Zinc Finger Protein 64 (ZFP64), a transcriptional factor, is implicated in cancer development and progression.
- This study investigates ZFP64's role in regulating BC stem cell-like properties and tumorigenesis via the glycolytic pathway.
Purpose Of The Study
- To determine if ZFP64 regulates stem cell-like properties and tumorigenesis in breast cancer.
- To elucidate the mechanism by which ZFP64 influences these processes, specifically focusing on the glycolytic pathway.
- To explore the potential of targeting ZFP64 and glycolysis for BC treatment.
Main Methods
- Analysis of ZFP64 expression in BC specimens and correlation with clinical data.
- In vitro assays (CCK8, colony formation, mammosphere formation) to assess cell viability, proliferation, and stemness.
- In vivo subcutaneous xenograft models to evaluate tumor growth and proliferation markers (Ki67).
- mRNA sequencing (mRNA-seq), Chromatin Immunoprecipitation (ChIP), and dual-luciferase reporter assays to investigate ZFP64's transcriptional activity on glycolysis-related genes.
- Glycolytic function assays measuring glucose consumption, lactate, and ATP production.
Main Results
- ZFP64 was overexpressed in BC tissues, correlating with shorter survival and advanced clinical stages.
- ZFP64 knockdown reduced BC cell viability, colony formation, and tumor growth in vivo, while ZFP64 overexpression had opposite effects.
- ZFP64 depletion inhibited stem cell-like properties, indicated by reduced mammosphere formation and downregulation of stemness markers (OCT4, Nanog, SOX2) and CD44+/CD24- subpopulations.
- ZFP64 directly binds to promoters of glycolysis genes (ALDOC, ENO2, HK2, SPAG4), activating their transcription and promoting glycolysis.
- Inhibition of glycolysis by targeting ENO2/HK2 suppressed ZFP64-induced proliferation and stem cell-like properties.
Conclusions
- ZFP64 promotes stem cell-like properties and tumorigenesis in breast cancer.
- This promotion is achieved by ZFP64 activating the glycolytic pathway through direct transcriptional regulation of key glycolytic genes.
- These findings highlight ZFP64 as a potential therapeutic target for breast cancer, with interventions aimed at glycolysis offering a promising strategy.
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