[대학원 생명과학과 세미나 안내]
연사 : 김준 교수(KAIST 의과학대학원)
연제 : YAP mediates drug resistance and immune evasion in melanoma
일시 : 2017년 9월 8일 (금) 오후 5시
장소 : 하나과학관 A동 B131호
초청교수 : 최의주 교수
Abstract
YAP is a transcriptional co-activator that plays key roles in controlling tissue growth, regeneration, and stem cell homeostasis. Multiple functions of YAP in tumor initiation and progression have recently been reported. Moreover, aberrant activation of YAP has been recognized as one of the key resistance mechanisms to BRAF inhibitors (BRAFi) in melanoma. In this study, we show that YAP activation drives evasion of BRAFi-resistant melanoma cells from CD8+Tcellimmuneresponses.WefoundthattheexpressionofimmunecheckpointligandsisupregulatedinBRAFi-resistantmelanomacellsandthattheupregulationisdependentonYAPactivity. YAP binds to enhancer regions of the genes encoding immune checkpoint ligands, and interaction between YAP and the transcription factor TEAD is essential for the YAP-mediated transcriptional upregulation. In addition, we demonstrate that both BRAFi-resistant and constitutively active YAP-expressing melanoma cells can suppress cytotoxic effect and cytokine production of tumor-specific CD8+Tcells.Immunohistochemical staining of tumor specimens from 65 melanoma patients reveals that nuclear YAP localization is associated with increased expression of immune checkpoint ligands in melanoma cells. Our findings suggest that YAP provides a mechanistic link between BRAFi resistance and immune evasion in the course of BRAFi treatment.