CD24 negativity reprograms mitochondrial metabolism to PPARα and NF-κB-driven fatty acid β-oxidation in
Divya Murthy1, Debasmita Dutta1, Kuldeep S Attri1
1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Cancer Letters
|February 19, 2024
Summary
CD24 acts as a tumor suppressor in metastatic triple-negative breast cancer (TNBC). Low CD24 expression promotes fatty acid oxidation, offering new therapeutic targets for TNBC.
Area of Science:
- Oncology
- Molecular Biology
- Metabolic Research
Background:
- CD24 is a known breast cancer stem cell (BCSC) marker, with CD24-negative/CD44-positive cells linked to metastasis.
- The specific function of CD24 in triple-negative breast cancer (TNBC), particularly its role in oncogenic signaling and metabolic changes, remains unclear.
Purpose of the Study:
- To investigate the functional role of CD24 in metastatic triple-negative breast cancer (TNBC).
- To elucidate the impact of CD24 expression on TNBC cell metabolism and oncogenic pathways.
Main Methods:
- Utilized CD24 knockdown and overexpression models in TNBC cell lines for in vitro and in vivo studies.
- Performed in silico gene expression analysis, lipidomic, and metabolomic profiling.
- Validated findings using reverse-phase protein array and xenograft models.
Main Results:
- CD24 functions as a tumor suppressor in metastatic TNBC.
- CD24 negativity upregulates mitochondrial oxidative phosphorylation and shifts TNBC metabolism towards fatty acid beta-oxidation (FAO).
- CD24 silencing activates PPARα and the CD24-NF-κB-CPT1A pathway, regulating FAO.
Conclusions:
- CD24 plays a novel role in the metabolic reprogramming of TNBC.
- Targeting CD24-mediated metabolic pathways presents a potential new therapeutic strategy for metastatic TNBC patients.
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