UC San Diego

Glioma is the most prevalent and highly malignant form of adult brain cancer and is exceedingly difficult to manage. Neural stem cells and glial-determining factors have recently been implicated in glioma formation. Key transcriptional regulators of developmental glial genesis are expressed in glioma and have functional roles during glioma tumorigenesis. Nuak2, has been shown to be upregulated in many cancers and result in metastasis. However, the role of Nuak2 in glioma is not well defined. Using a combination of in vitro and in vivo studies, we found that loss of Nuak2 via CRISPR-mediated deletion results in decreased proliferation, migration, and tumorigenicity in glioma cell lines. Further, in a IUE mouse model of glioma CRISPR targeted deletion of Nuak2 resulting in increased survivability while over-expression of Nuak2 lead to faster tumor progression and death. Together, these studies demonstrate that Nuak2 has a vital role in glioma tumorigenicity and lays the groundwork for more in-depth mechanistic studies.