Abstract B48: Ovarian cancer risk in laying hens is reduced by dietary polyunsaturated fatty acids: Implications for soluble E-cadherin, de novo lipogenesis, and mitochondrial metabolism

Aim: The specific aim of our research is to understand the relationship between soluble E-cadherin (sE-cad) expression, de novo lipogenesis, and mitochondrial metabolism in ovarian tumors from White Leghorn laying hens, in response to enrichment with diets that contain high levels of polyunsaturated fatty acids (PUFAs). Background: The shedding of the 80 kd extracellular domain of E-cadherin (E-cad) causes the production of sE-cad, which is implicated as a putative ligand for growth, survival, and angiogenesis in solid tumors. Little is known with regard to the relationship between sE-cad production and de novo lipogenesis or mitochondrial metabolism in ovarian tumors. De novo lipogenesis has been argued to be indispensable for their growth and proliferation. Vast physiologic research indicates that de novo lipogenesis is inhibited by PUFAs, indicating that dietary PUFAs could provide negative feedback to an essential metabolic pathway in ovarian tumors. Epidemiologic studies of human populations indicate that ovarian cancer (OvCa) risk is reduced 30-40% by high dietary consumption of omega-3 or omega-6 PUFAs. Hypothesis: We hypothesize that high dietary PUFA consumption downregulates de novo lipogenesis in ovarian tumors of laying hens, correlating with reduced sE-cad production and increased mitochondrial oxidative phosphorylation (OXPHOS) capacity. Methods: We used qPCR to measure genes related to de novo lipogenesis and mitochondrial OXPHOS. Gas chromatography was used measure the fatty acid content in ovarian tumors. Western blot was used to measure E-cad protein fragments. Results: Our lab observed a 20-40% reduction of OvCa risk in laying hens that were supplemented with whole flaxseed, flaxseed oil, corn oil or fish oil. qPCR results indicate reduced expression of genes related to de novo lipogenesis (i.e., Fatty Acid Synthase). Gas chromatography results indicate that the content of C16:0, C18:0 and C18:1 fatty acids is similarly reduced by dietary PUFA enrichment. qPCR results also indicate increased expression of the catalytic subunits for complexes 3, 4, and 5 of the mitochondrial electron transport chain when diets are enriched with PUFAs. Lastly, although the expression of E-cad protein was unaffected by diet, we did detect a significant reduction of the 37 kd carboxy-terminal fragment of E-cad (CTF1-Ecad) in the fish oil diet. This is an important finding, because CTF1-E-cad is the complementary fragment of sE-cad. Conclusions: OvCa risk in hens is reduced by consumption of omega-3 and omega-6 PUFAs, and these risk reductions associate with reduced de novo lipogenesis, reduced CTF1-E-cad expression, and improved mitochondrial OXPHOS capacity. This study reveals an additional anti-ovarian cancer mechanism of a flaxseed-supplemented diet. (NIH-RO1AT005295) Citation Format: Chris Weston, Matthew Young, Karen Hales, Dale Buchanan Hales. Ovarian cancer risk in laying hens is reduced by dietary polyunsaturated fatty acids: Implications for soluble E-cadherin, de novo lipogenesis, and mitochondrial metabolism [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B48.