Fig. 7

Model depicting the anti-HCC actions of PF-543. Elevated pro-angiogenic factors, exemplified by VEGF-A, act through their receptors to drive sprouting angiogenesis in tumor endothelial cells (EC), promoting tumor neovascularization and HCC progression. PFKFB3 serves as a molecular switch in this process, dictating the glycolytic energy supply that is essential for sprouting angiogenesis. The selective SphK1 inhibitor PF-543 abrogates S1P production, subsequently turning off the PFKFB3-mediated glycolytic switch, which leads to the inhibition of sprouting angiogenesis and eventually suppression of HCC progression. The graphical abstract was created with BioRender.com. . The 3D conformer of PF-543 was adapted from PubChem, pubchem.ncbi.nlm.nih.gov, CID 66,577,038