PFK-158 Increases Migration by Promoting Lipolysis and Fatty Acid Oxidation
Open Access
- Author:
- Bekker, Jennifer
- Area of Honors:
- Biology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Emily Sophia Bell, Thesis Supervisor
Michael Axtell, Thesis Honors Advisor - Keywords:
- Epithelial-mesenchymal transition
EMT
PFK-158
metastasis
cell migration
cell proliferation
cancer cell metabolism
lipid metabolism
AMPK
HGF - Abstract:
- Effective cancer therapies require stopping both the rapid growth of tumor cells and their ability to metastasize to other sites of the body, which can be promoted by the pro-migratory process of epithelial-mesenchymal transition (EMT). The newly developed therapeutic PFK-158 has been previously studied as an inhibitor to glycolysis on cell proliferation, but little is known about how it affects EMT and cell migration. Here we analyzed the inhibitor’s effect on cell proliferation and migration and noted that like hepatocyte growth factor (HGF)-induced EMT, PFK-158 promotes mesenchymal characteristics in cells such as inducing an elongated shape and increased cell migration and most likely does so by breaking down the cell-cell adhesions proteins between cell junctions. Furthermore, in both HGF and PFK-158-induced EMT, the AMP-activated protein kinase (AMPK) regulator of lipid metabolism is activated and cells re-localize lipid droplets towards the outer protrusions of the cell’s periphery, consistent with a metabolic shift to favor beta-oxidation of fatty acids from lipid droplets for energy. Overall, we discovered that cells undergoing EMT most likely shift their cell metabolism to energy production from lipolysis, and that PFK-158 could unexpectedly promote increased migration and metastasis by reprogramming lipid metabolism.