Emerging oncogene ATAD2: Signaling cascades and therapeutic initiatives

Abstract

ATAD2 is a promising oncoprotein with tumor-promoting functions in many cancers. It is a valid cancer drug-target and a potential cancer-biomarker for multiple malignancies. As a cancer/testis antigen (CTA), ATAD2 could also be a probable candidate for immunotherapy. It is a unique CTA that belongs to both AAA+ ATPase and bromodomain family proteins. Since 2007, several research groups have been reported on the pleiotropic oncogenic functions of ATAD2 in diverse signaling pathways, including Rb/E2F-cMyc pathway, steroid hormone signaling pathway, p53 and p38-MAPK-mediated apoptotic pathway, AKT pathway, hedgehog signaling pathway, HIF1α signaling pathway, and Epithelial to Mesenchymal Transition (EMT) pathway in various cancers. In all these pathways, ATAD2 participates in chromatin dynamics, DNA replication, and gene transcription, demonstrating its role as an epigenetic reader and transcription factor or coactivator to promote tumorigenesis. However, despite the progress, an overall mechanism of ATAD2-mediated oncogenesis in diverse origin is elusive. In this review, we summarize the accumulated evidence to envision the overall ATAD2 signaling networks during carcinogenesis and highlight the area where missing links await further research. Besides, the structure-function aspect of ATAD2 is also discussed. Since the efforts have already been initiated to explore targeted drug molecules and RNA-based therapeutic alternatives against ATAD2, their potency and prospects have been elucidated. Together, we believe this is a well-rounded review on ATAD2, facilitating a new drift in ATAD2 research, essential for its clinical implication as a biomarker and/or cancer drug-target.