Fig. 2: Connections among lipid regulatory pathways, signaling lipids and the invasive and metastatic phenotypes of tumor cells.

SREBP signaling and the PI3K/AKT/mTORC axis are mainly responsible for lipid anabolic metabolism, and the AMPK/ACC and SIRT1/PGC1α axes contribute to lipid catabolic metabolism in tumor cells. Accumulating signaling lipids, such as FAs, eicosanoids, PIs, sphingolipids and FABPs, represent causal factors for the cancer cell EMT program, the maintenance of the CSC subpool, the increased number of CTCs and the metastatic phenotype. CSC cancer stem cell, CTC circulating tumor cell, EETs epoxyeicosatrienoic acids, EMT epithelial–mesenchymal transition, FAs fatty acids, FABPs fatty acid-binding proteins, LTs leukotrienes, PGs prostaglandins, PIs phosphatidyl inositides, ACC acetyl-CoA carboxylases, Alox5 arachidonate 5-lipoxygenase, AMPK AMP-activated protein kinase, COX cyclooxygenase, FABPs fatty acid-binding proteins, LOX lipoxygenase, mTOR mammalian target of rapamycin, PG prostaglandin, PI3K phosphoinositide 3-kinase, SREBP sterol regulatory element-binding proteins, SPHK1 sphingosine kinases