ATAD2 Drives Melanoma Growth and Progression and inhibits Ferroptosis

ABSTRACT: Melanoma is a highly metastatic form of skin cancer for which current therapies offer limited benefits. We identify that the histone reader ATAD2 is overexpressed in melanoma and predicts poor prognosis. We show that the MAP kinase pathway, via the transcription factor E2F1, stimulates ATAD2 expression. Genetic or pharmacological inhibition of ATAD2 suppresses the growth and metastasis of BRAF and NRAS mutant melanoma. Mechanistically, we find that ATAD2 inhibition activates both distinct and common tumor-suppressive pathways in BRAF and NRAS mutant melanoma. In particular, we found that the inhibition of ATAD2 induces ferroptosis in both contexts by downregulating the ferroptosis suppressor GPX4. Furthermore, the ferroptosis inducer erastin effectively inhibits melanoma growth. Combining

SUBMITTER: Romi Gupta 

PROVIDER: S-SCDT-10_1038-S44319-025-00660-W | biostudies-other |

REPOSITORIES: biostudies-other