RELA and central nervous system cancer: Current therapeutic strategies for targeting NF-κB signaling in high-grade glioma, as well as other tumors, focus on inhibition of the canonical/p65-mediated pathway,49 which has well-established tumor-promoting functions.50, 51 Here, we have established new roles for NIK in regulating MT1-MMP activity and tumor cell invasion that are independent of RelA/p65, underscoring the importance of developing treatment strategies that target both the canonical and noncanonical NF-κB pathways.