Chromosomal 3p loss and 8q gain drive vasculogenic mimicry via HIF-2α and VE-cadherin activation in uveal melanoma.

ABSTRACT: Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults and is where Vasculogenic Mimicry (VM) was first described. VM enables aggressive cancer cells to independently form blood networks, complicating treatment for patients exhibiting VM. Previous studies linked VE-Cadherin phosphorylation at Y658 to gene expression via Focal Adhesion Kinase (FAK), enhancing the Kaiso/β-catenin/TCF-4 complex associated with VE-Cadherin and thereby promoting VM. Recently, an allosteric HIF-2α inhibitor (Belzutifan) was FDA-approved for VHL-associated ccRCCs. In this research, we elucidate the primary causes of VM formation in UM patients with chromosome 3p loss and chromosome 8q gain, identifying VHL, BAP1, and FAK as important factors driving VM and worsening prognosis. These

SUBMITTER: Delgado-Bellido D 

PROVIDER: S-EPMC12325912 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature