BMC Seminar Thursday, 14th April at 12:25 Room 343 Læknagarður
Speaker: Katrín Möller, MSc student at Eiríkur Steingrímsson´s lab, Biomedical Center, Faculty of Medicine, University of Iceland
Title: The role of the Microphthalmia associated transcription factor in autophagy regulation in melanoma
Abstract: Autophagy is considered a therapeutic target in various cancer types, including melanoma. The transcription factors TFEB and TFE3 have been shown to play a key role in autophagy regulation in various cell types by affecting gene expression required for this process. A close relative to these factors is the transcription factor MITF, the master regulator of melanocyte development and of melanoma.
Analysis of available MITF ChIP sequencing data shows that MITF binds promoters of lysosomal genes in melanoma cells, and ChIP experiments in 501Mel melanoma cells show binding to autophagy and lysosomal genes. Analysis of The Cancer Genome Atlas expression data from melanoma tumors reveals that MITF expression correlates with lysosomal gene expression in metastatic tumors. Further analysis of expression data of 24 melanoma cell lines also shows MITF correlation with lysosomal gene expression. We also observed this experimentally by over-expression and knock down experiments in SKMel28 and 501Mel melanoma cells. In addition this process was assayed in a SKMel28 MITF knock down cell line which was generated using the CRISPR/Cas9 technique, showing an altered autophagy response to starvation.
Autophagy is high in melanoma and has been linked to tolerance against cancer treatment. We have found that MITF regulates autophagy genes and activity in melanoma cell lines. In light of both MITF and autophagy being considered a therapeutic target in melanoma, this relationship needs to be taken into consideration.