Deciphering functional intra-tumoral heterogeneity in BRAFV600E-driven mouse thyroid cancer reveals EMT trajectory and metabolic remodeling - PubMed
6 hours ago
- #EMT trajectory
- #BRAFV600E
- #metabolic remodeling
- Single-cell RNA sequencing in a BRAFV600E-driven mouse thyroid cancer model reveals functional intra-tumoral heterogeneity.
- An EMT trajectory is identified where malignant cells progress from intermediate to more mesenchymal and malignant states.
- Subpopulations maintain distinct EMT states via specific pathways, with transitioning cells showing dynamic molecular shifts.
- Metformin reduces the most malignant subpopulation and inhibits EMT potential in cultures and the mouse model.
- p53 deficiency lowers the tumorigenic threshold for BRAFV600E, promoting transition to a more malignant state without altering heterogeneity or trajectory.
- Findings have clinical relevance, with an EMT-related gene module predicting outcomes in human BRAFV600E PTCs.
- The study provides a foundation for developing EMT-targeted treatments in thyroid cancer.