Lipid Metabolism in Cancer Development and Treatment
It has been well documented that cancer cells alter their metabolism to suit their needs for uncontrolled proliferation. One of the metabolic changes frequently found in cancer cells is increased fatty acid synthesis, which is most clearly demonstrated in clear cell renal cell carcinoma (CCRCC) that accounts for ~80% of kidney cancers (Fig. 1). However, the functional significance of this metabolic alteration for cancer development remains unclear.
Our recent identification of the UAS domain as a motif interacting with fatty acids may provide a clue to answer this question. It turns out that mammalian cells express two UAS domain-containing proteins, namely FAF1 and Ubxd7 that potentially inhibit development of CCRCC. FAF1 is a potent tumor suppressor, the expression of which is silenced in various tumors but not in CCRCC. Ubxd7 is required for proteasomal degradation of HIFa subunits, the aberrant accumulation of which is believed to initiate CCRCC development. So is it possible that increased production of fatty acids is required to inhibit FAF1 and Ubxd7 to facilitate development of CCRCC? This hypothesis is currently actively pursued in my lab. We are also interested in identifying the mechanism behind increased synthesis of fatty acids in CCRCC cells. The ultimate goal of the project is to find a way to treat CCRCC by targeting the abnormal lipid metabolism in these cancer cells.