Role of Stearoyl-CoA desaturase-1 in cell proliferation, survival and tumorigenesis of A549 human lung adenocarcinoma cells

N. SCAGLIA; R. A. IGAL

Congreso; Annual Retreat on Cancer Research in New Jersey; 2007

Saturated (SFA) and monounsaturated (MUFA) fatty acids, the most abundant fatty acid species, have many divergent biological effects including regulation of cell proliferation, programmed cell death, and lipid-mediated cytotoxicity. Their distribution is regulated by Stearoyl-CoA Desaturases (SCD), the enzymes that convert SFA into MUFA. A positive correlation between high levels of MUFA and several types of cancer has been reported, but a causal relationship between the function of SCD1, the main human SCD isoform, and cancer development has not been firmly established yet. Here we report that the stable knockdown of SCD1 gene expression in A549 human lung adenocarcinoma cells decreases the ratio SFA/MUFA in lipids and reduces the incorporation of SFA into phospholipids while increasing SFA acylation into triacylglycerol. Interestingly, cell proliferation and anchorage-independent growth was considerably reduced in SCD1-depleted cells with respect to control A549 cells and could not be reversed by exogenously added oleic acid, the product of SCD activity. In addition, the rate of apoptosis in SCD1-ablated cells was increased when compared to mock-transfected control cells. Remarkably, the ablation of SCD1 expression in lung cancer cells significantly delayed the formation of tumors and reduced the growth rate of tumor xenografts in mice. Our study suggests that SCD1 activity determines the rate of cell proliferation, survival and invasiveness in lung cancer cells and shows, for the first time, that SCD1 is a key factor in the regulation of tumorigenesis in vivo.