Presentation description

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy of the adrenal cortex with ineffective treatment options and high mortality rates. Wnt signaling, which involves a group of highly conserved ligands regulating cellular fate and tissue development, is broadly activated in ACC; however, analysis of tumor datasets identifies WNT5A as the predominant ligand driving this activation. In this study, we experimentally demonstrate that loss of Wnt5a significantly lowers tumor incidence and increases tumor-free survival in a mouse model. Furthermore, analysis of clinical data shows that ACC patients with high WNT5A expression exhibit poor outcomes, highlighting the clinical relevance of our findings. Our results suggest that targeting WNT5A may hold therapeutic potential for improving outcomes in ACC patients.