Ketomimetic Nutrients Trigger a Dual Metabolic Defense in Breast Cancer Cells

Area of Science:

• Oncology
• Cell Biology
• Metabolic Research

Background:

• Metastatic transformation of breast cancer (BC) is poorly understood, but cellular metabolism may drive invasiveness and chemoresistance.
• Investigating metabolic reprogramming in BC is crucial for understanding metastasis and developing targeted therapies.

Purpose of the Study:

• To investigate how a ketomimetic medium affects Doxorubicin (DOX) susceptibility and invasive potential of BC cells.
• To elucidate the molecular mechanisms underlying metabolic adaptation in BC cells.

Main Methods:

• Quantification of glycocalyx sialylation.
• Single-cell metabolic imaging.
• Bulk migration assays.
• Transcriptomic and metabolomic analyses.

Main Results:

• A ketomimetic medium inversely correlated with DOX-induced cytotoxicity and DOX internalization, indicating enhanced chemoresistance.
• Ketomimetic conditions led to hypersialylation and increased lipid synthesis in BC cells.
• These pathways converge at UDP-GlcNAc synthesis, promoting a metastatic phenotype.

Conclusions:

• Ketomimetic medium enhances BC chemoresistance and invasiveness through hypersialylation and lipid synthesis.
• Metabolic reprogramming via ketomimetic diet may promote BC metastasis.
• Targeting the crosstalk between sialylation and lipid synthesis pathways could offer novel therapeutic strategies for metastatic BC.