MERTK: upstream from BRAF

Abstract

(AXL; UFO). MERTK is expressed on at least three types of normal cells: platelets, for which it aids their aggregation; macrophages, which it enables to engulf target cells; and a range of epithelial cell types, for which it plays a role in survival. Studies by multiple groups have shown that MERTK is overexpressed or hyperactivated—and thus a potential therapeutic target—in leukemia 2 and in prostate, 3 brain 4 and lung 5 cancers. At least one study has shown that TAM and other tyrosine kinase receptors are activated in melanoma, 6 and two more have linked TYRO3, AXL and the TAM receptor ligand, growth arrest–specific 6 (GAS6), to melanoma tumorigenesis and invasiveness. 7,8 Collectively, these findings prompted Douglas Graham and colleagues to hypothesize that MERTK might also be a therapeutic target in melanoma. Graham is assistant professor of pediatrics and immunology at the University of Colorado Denver School of Medicine. To investigate this hypothesis, Graham's team performed microarray analyses and found that MERTK was overexpressed in about 50% of melanomas compared with normal human melanocytes. Moreover, there was higher MERTK expression in metastatic melanoma than in primary tumors.