A BRN2:MYC transcriptional axis regulates interconversion between therapy-resistant and tumorigenic phenotypes in melanoma.

ABSTRACT: Metastatic spread and therapeutic resistance are the principal causes of cancer mortality. For melanoma, these processes rely on the capacity of cells to switch between transcriptional states. Although targeting transcriptional states pharmacologically is promising, the mechanisms by which melanoma cells switch between states-and how these processes differ from melanocytes-remain poorly understood. Here, we isolate distinct melanoma states with unique phenotypes: a MYC-driven state, essential for tumor initiation yet sensitive to BRAF inhibition, and a dedifferentiated, invasive BRN2-high state enriched in therapy-resistant cells but not directly tumorigenic. Transitions between phenotypes occur through intermediate, more differentiated states. Unexpectedly, the BRN2-high state is also pre

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12834598 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature