Here, we demonstrate that Nuclear Factor I A (NFIA) transcriptionally upregulates SMC4 expression, and elucidate a dual mechanistic role for SMC4 in glioma progression: (1) promotion of metastatic potential via enhancement of TGF-β/Smad signaling transduction; and (2) facilitation of aerobic glycolysis through upregulation of LDHA. This evidence concerns the gene NFIA and central nervous system cancer.