PMC

(A) AXL consists of two immunoglobulin-like (Ig) domains and dual fibronectin type III (FNIII) repeat domains and a kinase domain. Gas6 contains a γ-carboxyglutamic acid (Gla) domain, a loop region, four EGF-like repeats and two C-terminal globular laminin G-like (LG) domains. (B) AXL can be activated by ligand-dependent dimerization, ligand-independent dimerization, and interaction between two monomers on neighboring cells and heteromeric dimerization with a non-TAM receptor. (C) AXL plays important roles in cell proliferation, survival, migration, and the inflammatory process via different signaling pathways.

(A) EGFR TKI sensitive cells are EGFR signal dependent in survival and proliferation. (B) EGFR and AXL collectively regulate survival and proliferation in acquired EGFR TKI resistant cells. (C) A switch from an EGFR pathway dependent signal transduction pattern to an AXL/MET complex dependent pattern plays critical roles in acquired EGFR TKI resistance correlated EMT. AXL/MET over-expression, GAS6/HGF up-regulation, MET amplification, and AXL/MET might mediate uncoupling of EGFR activity from its kinase function and are reported causes of this switch to EGFR signaling independence.