Engineered AXL^-ECD-Fc variants that abolish the AXL/Gas6 interaction suppress tumor cell migration.

ABSTRACT: AXL receptor tyrosine kinase ligand (AXL), a tyrosine kinase receptor that is commonly overexpressed in numerous types of cancer, significantly promotes drug resistance and metastasis in tumor cells. Inhibition of the AXL/growth arrest-specific 6 (Gas6) signaling pathway is emerging as a potential anticancer therapeutic strategy. In the present study, on the basis of the three-dimensional complex structure of AXL/Gas6, the critical residues (E⁵⁶, E⁵⁹ and T⁷⁷) in AXL binding to Gas6 were determined using computer graphics analysis and the distance geometry method. Subsequently, four-variant AXL^-ECD-Fc-M1 (G³²S, D⁸⁷G, V⁹²A and G¹²⁷R) and AXL^-ECD-Fc-M2 (G³²A, D⁸⁷A, V⁹²

SUBMITTER: Duan Y 

PROVIDER: S-EPMC6507473 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature