Taken together, both in vitro and in vivo experimental results summarize that glycolytic reprogramming of impaired PFKFB3 by PFK158 treatment or genetic KD inhibits cancer stemness, migration/invasion, and resistance via regulating critical factors of CSC, EMT, and multidrug resistance, which then led to abolished tumor establishment (Fig. 8). The gene discussed is PFKFB3; the disease is cancer.