RARE-21Sox2 plays an important role in choroid plexus tumor development

Choroid plexus (CP) tumors are rare primary brain neoplasms found most commonly in children and are thought to arise from CP epithelial cells. Sox2 is a transcription factor that not only plays a role in development in the ventricular zone, CP, and roof plate, but also contributes to cancer stemness, tumorigenesis, and drug resistance. Gene expression studies demonstrate aberrant Sox2 expression in human CP tumors, suggesting a role in tumor development. A subset of CP tumors exhibit abnormal NOTCH pathway activity. Using animal models, we previously show that sustained NOTCH activity leads to CP tumors. Immunofluorescence, RT-qPCR, and RNA scope assays have revealed increased Sox2 levels in NOTCH-driven CP tumors compared to wild type CP in mice. To investigate the role of Sox2 in CP tumors, we eliminated Sox2 expression in NOTCH-driven CP tumors. Loss of Sox2 almost completely blocked NOTCH-driven CP tumor growth in these mice, supporting a role for Sox2 in these tumors. Ciliation regulation is one proposed functional pathway for tumorigenesis in CP tumors. Using immunofluorescence assays for cilia (ARL13b) and aquaporin transport protein 1 (AQP1) in combination with super resolution microscopy, we observe a stark contrast between wild type CP epithelial cells which are multiciliated and homogeneously express AQP1, indicative of normal epithelial differentiation, compared to NOTCH-driven CP tumors consisting of mono-ciliated cells with loss of AQP1 expression. In Sox2-deficient NOTCH-driven CP tumors, we observe tumor cells remain mono-ciliated and AQP1-negative, indicating that Sox2 loss does not affect the ciliation machinery. Together this warrants further study into the mechanisms of Sox2 functions in CP tumors. By unraveling the role of Sox2 in CP tumors, we may better understand their origin and biology to ultimately design improved treatment options.