Oncogenic insult to the brain: sox proteins rise to the occasion

The concept of cancer stem or stem-like cells has changed thinking and approaches in oncology just as much as the discovery of stem cells did in developmental biology and regenerative medicine before. Glioblastoma multiforme (GBM) as the most frequent and malignant primary brain tumor with an extremely poor prognosis is a case in point (1). So-called glioma stem-like cells (GSCs) are thought to originate from neural stem cells (NSCs) and play an important role in GBM initiation (2). The transcriptional network of GSCs still bears resemblance to the one of normal NSCs. However, during malignant transformation changes occur that deregulate expression of neural stem cell traits (3) and factors such as complexes consisting of cyclins and cyclin-dependent kinases (CDK), CDK inhibitors (CDKi) and p53 (4,5), which in turn influence proliferation, cell cycle, mode of division and decisions to self-renew or differentiate. Levels of CDKi and p53 are, for instance, usually low in GSCs and GBM. Their increase in normal NSCs counteracts and prevents malignant cell transformation upon oncogene-based cellular stress (6,7)