Dead-End protein expression, function, and mutation in cancer: a systematic review

Cancer incidence is rising globally, particularly in aging populations. Understanding the genetic, cellular, and molecular mechanisms underlying cancer is crucial for developing effective interventions. Dead-end protein 1 (DND1), an RNA-binding protein, plays a pivotal role in germ cell regulation and tumorigenesis. This systematic review investigates DND1's multifaceted roles in cancer progression and evaluates its interactions and potential as a therapeutic target. A systematic search of four databases (Web of Science, MEDLINE via PubMed, Scopus, and Embase) yielded 436 unique records. After screening, 38 studies were included for data extraction. STRING-based network analysis identified key interactors-including NANOS1-3, TDRD7, DAZL, and EIF2S2- and pathways associated with RNA binding, translational regulation, and apoptosis. DND1 demonstrates dual, context-dependent roles as both a tumor suppressor and promoter. Its regulation of miRNAs and interaction with germ cell-specific proteins emerged as critical mechanisms in tumor suppression and progression. This study highlights DND1's central role in cancer biology, with significant implications for diagnostics and therapeutics. The findings provide a robust foundation for experimental validation of key interactions and further exploration of DND1's molecular mechanisms. The dual functionality of DND1 as a tumor suppressor and promoter underscores its potential as a target for novel cancer therapies, particularly for germ cell tumors and other cancers.