Our results show that PFKFB3-mediated targeting by PFK158 or genetic manipulation resulted in inhibition of glycolysis (Fig. 3a–h) and of tumor progression (Fig. 7a–d), resulting in diminished cancer “stemness” by decreasing both surface and intracellular stem cell marker expressions such as CD133, CD44, Aldh1, and Sox2 (Fig. 1a–f). Here, PFKFB3 is linked to cancer.