Investigating the relationship Between AMBRA1 and Cell Proliferation in Melanoma

Abstract

The protein Activating molecule in Beclin1-regulated autophagy1 (AMBRA1), discovered in 2007, is crucial for autophagy and plays roles in nervous system development, cell survival, and proliferation. This study investigates AMBRA1s involvement in various cellular processes using a systems-based "omics" approach, focusing on melanoma. Transcriptomic analysis of the overexpression or the knock-down of AMBRA1 was shown to result in significant dysregulation of several transcripts. This appears to have identified several novel roles for AMBRA1 in a range of cellular pathways; some of these are hallmarks of cancer signaling including, MAPK, angiogenesis, tissue growth factor signaling, axon guidance and Wnt signaling. Yeast two-hybrid assays performed in this study identified novel binding partners that can provide evidence for new roles for AMBRA1 in different cellular processes. The work shows that AMBRA1 loss appears to upregulate metastatic genes/proteins supporting the role of AMBRA1 as a tumor suppressor gene in melanoma.