Reconfiguration of Lipid Metabolism and SCAP-SREBP Pathway in Endometrial Carcinoma

Endometrial cancer (EC), a leading malignancy in women, has seen rising incidence and decreasing age of onset globally, turning it into a significant health concern. Postmenopausal uterine bleeding is a key early sign, enabling prompt diagnosis. EC risk factors include hormonal influences, metabolic disorders, and genetic predispositions. Recent studies have unveiled the vital role of fatty acid metabolism reprogramming in cancer initiation and progression. This research focuses on the gene expression of lipogenesis-related molecules –SREBP cleavage-activating proteins (SCAP), Sterol Regulatory Element Binding Protein (SREBP), Stearoyl-CoA Desaturase (SCD), and Fatty Acid Synthase (FASN)– in endometrial cancer tissues. Using real-time PCR, we analyzed 54 EC patients and 36 healthy controls. The results reveal a significant upregulation of SCAP, SREBPF1, FASN, and SCD in cancerous tissues compared to controls (p< 0.05). Additionally, FASN (p= 0.014) and SCD (p= 0.0001) expression levels were markedly higher in the proliferative phase of controls. These findings highlight the reprogramming of lipid metabolism as a critical driver in EC progression. A deeper understanding of these metabolic pathways could lead to innovative therapies, making lipid metabolism a promising target for future cancer treatments. Keywords: Endometrial cancer, SCAP, SREBP, FASN, SCD