AKT1^E17K Activates Focal Adhesion Kinase and Promotes Melanoma Brain Metastasis.

ABSTRACT: Alterations in the PI3K/AKT pathway occur in up to 70% of melanomas and are associated with disease progression. The three AKT paralogs are highly conserved but data suggest they have distinct functions. Activating mutations of AKT1 and AKT3 occur in human melanoma but their role in melanoma formation and metastasis remains unclear. Using an established melanoma mouse model, we evaluated E17K, E40K, and Q79K mutations in AKT1, AKT2, and AKT3 and show that mice harboring tumors expressing AKT1^E17K had the highest incidence of brain metastasis and lowest mean survival. Tumors expressing AKT1^E17K displayed elevated levels of focal adhesion factors and enhanced phosphorylation of focal adhesion kinase (FAK). AKT1^E17K expression in melanoma cells increased invas

SUBMITTER: Kircher DA 

PROVIDER: S-EPMC6726552 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature