Cholesterol inhibits assembly and oncogenic activation of the EphA2 receptor.

ABSTRACT: The receptor tyrosine kinase EphA2 drives cancer malignancy by facilitating metastasis. EphA2 can be found in different self-assembly states: as a monomer, dimer, and oligomer. However, we have a poor understanding regarding which EphA2 state is responsible for driving pro-metastatic signaling. To address this limitation, we have developed SiMPull-POP, a single-molecule method for accurate quantification of membrane protein self-assembly. Our experiments reveal that a reduction of plasma membrane cholesterol strongly promotes EphA2 self-assembly. Indeed, low cholesterol levels cause a similar effect to the EphA2 ligand ephrinA1-Fc. These results indicate that cholesterol inhibits EphA2 assembly. Phosphorylation studies in different cell lines reveal that low cholesterol increased phospho-s

SUBMITTER: Schuck RJ 

PROVIDER: S-EPMC11897322 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature