Antony J1,2,3, Huang RY4,5,6.
1 Cancer Science Institute of Singapore, National University of Singapore, Singapore.
2 NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
3 Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
4 Cancer Science Institute of Singapore, National University of Singapore, Singapore. email@example.com.
5 Department of Obstetrics and Gynecology, National University Health System, Singapore.
6 Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
The receptor tyrosine kinase (RTK) AXL has been intrinsically linked to epithelial-mesenchymal transition (EMT) and promoting cell survival, anoikis resistance, invasion, and metastasis in several cancers. AXL signaling has been shown to directly affect the mesenchymal state and confer it with aggressive phenotype and drug resistance. Recently, the EMT gradient has also been shown to rewire the kinase signaling nodes that facilitate AXL-RTK cross-talk, protracted signaling, converging on ERK, and PI3K axes. The molecular mechanisms underplaying the regulation between the kinome and EMT require further elucidation to define targetable conduits. Therapeutically, as AXL inhibition has shown EMT reversal and resensitization to other tyrosine kinase inhibitors, mitotic inhibitors, and platinum-based therapy, there is a need to stratify patients based on AXL dependence. This review elucidates the role of AXL in EMT-mediated oncogenesis and highlights the reciprocal control between AXL signaling and the EMT state. In addition, we review the potential in inhibiting AXL for the development of different therapeutic strategies and inhibitors.