Phosphorylated T567 ezrin is associated with merlin expression in KIT-mutant gastrointestinal stromal tumors

Abstract

Membrane-cytoskeleton linker organizer ezrin is a member of the ERM (ezrin-radixin-moesin) protein family. It has been suggested as an important element in the oncogenic process, particularly in conferring a metastatic ability on tumor cells. We hypothesized that the KIT oncogenic form is one of the proteins that modulates expression of the ezrin protein via phosphorylated ezrin at different residues; furthermore, it may interact with the protein merlin, and promoting tumor development via the PI3K or MAPK pathway. In the present study, we observed that differential expression of ezrin was a common feature in gastrointestinal stromal tumors (GISTs). We further demonstrated that cases exhibiting expression of phosphorylated Thr567 in the ezrin protein were associated with immunoactivities of KIT and merlin expression (p=0.039 and 0.013, respectively). In conclusion, GISTs harbor activation of KIT protein may induce phosphorylation of the downstream protein ezrin at certain residues, thereby triggering subsequent signal transduction cascades and driving downstream pathways of tumor progression. However, a larger series of tumor samples should be analyzed in future studies, as well as the identification of phosphorylated sites to determine the role of ezrin in tumor progression thus shedding light on clinical outcomes.