Figure 3

Roles of PFKFB3 in different cancer cells. High levels of the PFKFB3 isoenzyme have been proven to promote the oncogenesis, proliferation and survival of cancer cells. Elevated PFKFB3 in CSCs has been estimated to be related to distant metastasis and poor clinical outcome. PFKFB3 is apparently induced by hypoxia in CSCs. Silencing of PFKFB3 impairs vessel sprouting due to defects in both migrating tip and proliferating stalk cells. PFKFB3, compartmentalized with F-actin in lamellipodia, provide ATPs for vascular sprouting, and VEGFR2 induces PFKFB3 and activates Notch signaling. Immune cells shift from OXPHO to glycolysis when activated. The TLR/PI3K/Akt signaling pathway controls this shift in DC cells. In T cells, PFKFB3 is induced downstream by the TCR/CD28 receptor. PFKFB3 expression is increased by the transcription factors HIF1α, C/EBPβ and Sp1 in macrophages, and the PFKFB3 enzyme is phosphorylated by AMPK.