NF-kB Inducing Kinase (NIK) Is an Inducer of Glioma Invasion

Abstract

Glioblastomas (GBMs) are a malignant subtype of brain tumor hallmarked by a high proliferation rate, cell migration, and aggressive invasion into healthy surrounding brain tissue. The extremely invasive phenotype of GBMs contributes exponentially to the high tumor recurrence and low median survival rate of patients. Our lab has demonstrated that NF- ҡB Inducing Kinase (NIK/MAP3K14), the primary driver of the noncanonical NF-ҡB pathway, is essential for glioma invasion and tumor formation. We have shown that abolishing NIK attenuates invasion, while cells with low NIK expression are significantly less invasive. Recent observations have shown that specific induction of NIK mRNA occurs in response to stimulation with pro-invasive cytokines (e.g. TNF-like Weak inducer of apoptosis). Here, we address the effects of increased NIK mRNA expression on glioma cell invasion and the effects of inhibition of NIK. We also examine NIK-dependent paracrine effects that promote a leader cell phenotype by enhancing the invasion potential of low invasive cells.