PAK5-Mediated Suppression of β-Hydroxybutyrate Production Promotes Breast Cancer Metastasis and Can Be Overcome with Ketogenic Diet - PubMed
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- #breast cancer
- #ketogenic diet
- #metastasis
- PAK5 suppresses β-hydroxybutyrate (β-HB) production, promoting breast cancer metastasis.
- β-HB levels are lower in breast cancer patients, especially those with metastasis.
- PAK5 inhibits β-HB synthesis by phosphorylating HMGCS2, a key enzyme in ketone generation.
- Phosphorylation at Ser138 and Ser311 on HMGCS2 reduces its stability and activity.
- High PAK5 levels correlate with breast cancer metastasis and poor clinical outcomes.
- Ketogenic diet (KD) or β-HB supplementation can counteract PAK5-driven metastasis.
- Low HMGCS2 expression and β-HB synthesis are linked to lymph node metastasis.
- PAK5-HMGCS2 pathway is a potential therapeutic target for breast cancer metastasis.