Therapeutic Targeting of Lipid Droplets as Disease Markers in Ovarian Cancer
Technical Report,15 Jun 2013,14 Dec 2015
Mayo Clinic Rochester United States
Pagination or Media Count:
It is increasingly being recognized that altered lipid metabolism is an early event in carcinogenesis and a central hallmark of many cancers. Under nutrient deprived conditions, excess free fatty acids are stored as triglycerides in lipid droplets LD to be used for energy. Microarray and Metabolomics profiling identified the lipid pathway as one the major pathways modulated by loss of HSulf-1 in ovarian cancer. HSulf-1 deficient cells OV202 Sh1sh2, OV2223 and Sulf-1 KO MEFs possess high levels of lipid droplets LD that are absent in the HSulf-1 proficient isogenic cells TOV21G and SKOV3. More importantly, TEM analysis showed that all HSulf-1 deficient cells displayed increased number of LDs compared to isogenic HSulf-1 proficient cells. Increased accumulation of LDs in HSulf-1 depleted cells was associated with increased ERK mediated cPLA2S505 phosphorylation, a well-known marker for lipid biogenesis. Pharmacological inhibition and ShRNA downregulation of cPLA2 activity, a protein involved in LD biogenesis resulted in decreasing the of LDs. Using mouse model of OV202 Sh1 derived xenograft, we show that AACOCF3 effectively attenuated tumor growth, LD biogenesis and reduced tumorigenesis in vivo.