SOLUBLE TAM RECEPTOR AXL TRIGGERS CHANGES IN CELL BEHAVIOR AND SIGNALING OF BLADDER CANCER CELLS

Abstract

AXL, a member of the TAM family, has emerged as a potential target for treating bladder cancer due to its role in cellular activities and tumorigenesis. This receptor was found to be overexpressed in cancer. Here, the soluble form of AXL (sAXL) is studied. sAXL has been proposed to act as a decoy receptor, which sequesters growth arrest-specific 6 (Gas6) ligand and shuts down Gas6/AXL axis. This hypothesis has been supported by several studies that demonstrated a high-affinity binding between sAXL and Gas6. Nevertheless, the role of sAXL in cellular signaling in bladder cancer has not been studied. This study investigated if sAXL affects cell behavior and signaling of bladder cancer cells and if it can act as a decoy. The recombinant AXL and Gas6 were used for the analysis, and cells were cultured with further incubation with these proteins. Western blotting was used to investigate the expression of AXL downstream targets. The findings revealed that sAXL has a similar effect on cells as Gas6, proposing that sAXL may participate in homophilic and heterophilic binding with TAM receptors. Moreover, sAXL sequestered Gas6 in pAkt-308 activation. As a future perspective, a broader analysis of the interactions between soluble AXL and TAM receptors is needed.