Y-Box Binding Protein-1: A Neglected Target in Pediatric Brain Tumors?

Abstract

Brain and central nervous system tumors represent the most common childhood solid tumors. Comprising 21% of all pediatric cancers, they remain the leading cause of cancer-related mortality and morbidity in childhood. Due to advances in neurosurgical technique, radiotherapy and the use of combination therapy, survival rates have generally increased. However, by cause of the lesion itself, its surgical removal and subsequent treatment, survivors are at high risk of long-term neurocognitive sequelae and secondary cancer. Clearly, improvements in diagnosis and treatment are needed. Accordingly, current treatment is evolving away from conventional, uniform therapy and towards risk-stratified regimens and molecularly-targeted therapies, with the aim of diminishing adverse side effects while minimizing the risk of disease recurrence. The multifunctional oncoprotein Y-box binding protein 1 (YB-1) may serve as one such molecular target. Increased YB-1 levels have been reported in a number of pediatric brain tumors, where YB-1 appears to facilitate the advancement of malignant phenotypes. These include proliferation, invasion, and resistance to therapy, as well as the maintenance of brain tumor-initiating cells. Here we evaluate the current literature and show how YB-1 modulates signaling pathways driving each of these phenotypes. We also review the regulation of YB-1 at a transcriptional, translational, posttranslational and subcellular level and argue that there is strong and sufficient evidence to support the development of YB-1 as a biomarker and future therapeutic target in childhood brain tumors.