LDHA-mediated CREB1 Lactylation Promotes Breast Cancer Brain Metastasis by Transcriptionally Activating Cytoskeletal Remodeling - PubMed
3 hours ago
- #lactylation
- #brain metastasis
- #breast cancer
- Identified a malignant epithelial sub-cluster (Cluster 3) with high lactate levels and superior brain metastasis potential.
- LDHA-mediated lactylation of CREB1 at K136 enhances its transcriptional activity, upregulating cytoskeletal genes (CALML5, CNN2, PDLIM1).
- CREB1 lactylation promotes pseudopodia formation and cellular migration, driving brain metastasis.
- In vivo, LDHA knockdown reduced intracranial tumor burden in mice.
- High lactylation scores and CALML5 expression are clinical predictors of brain metastasis and overall survival.
- The LDHA-lactylation-CREB1-cytoskeleton axis is a novel therapeutic target and prognostic biomarker for breast cancer.