교모세포종에서 STAT3-KRAS 신호를 통한 MerTK의 종양 줄기세포 유지 및 침윤성에 대한 기작 연구

Abstract

Glioma is the most common intracranial tumors. Despite modern diagnosis and treatment of glioma with chemotherapy, irradiation or surgery, the median survival time does not exceed 15 months. MerTK has been shown to be highly expressed in Glioblastoma multiforme (GBM) than normal counterpart and is involved in brain tumor progression. However, the signaling mechanisms by which MerTK contributes to relapse and invasion of GBM remain largely unknown. Here, I aimed to define the signaling mechanisms by which MerTK provides to maintenance of glioma stem-like cells (GSCs) and invasion of GBM cells. MerTK depletion effectively suppressed maintenance of GSCs as evidenced by a decrease in sphere forming ability and GSC markers including CD133, Musashi and SOX2. MerTK silencing also attenuates invasiveness of GBM cells. Importantly, MerTK caused an activation of SRC and STAT3 and particularly an increase in KRAS expression level, suggesting that MerTK contributes to tumor progression through these signaling pathways. Taken together, my findings demonstrate that MerTK acts as a critical player for maintenance of GSCs and invasiveness of GBM cells through KRAS, SRC and STAT3. Considering the low basal level of MerTK in normal brain, evaluation of MerTK as a therapeutic target merits further investigation to improve therapeutics.