| Autor: |
Melana JP; Laboratorio de Investigaciones Bioquímicas de la Facultad de Medicina (LIBIM), Instituto de Química Básica y Aplicada del Nordeste Argentino (IQUIBA-NEA), Universidad Nacional del Nordeste, Consejo Nacional de Investigaciones Científicas y Técnicas (UNNE-CONICET), Corrientes 3400, Argentina., Mignolli F; Instituto de Botánica del Nordeste, Facultad de Ciencias Agrarias (UNNE-CONICET), Universidad Nacional del Nordeste, Corrientes 3400, Argentina., Stoyanoff T; Laboratorio de Investigaciones Bioquímicas de la Facultad de Medicina (LIBIM), Instituto de Química Básica y Aplicada del Nordeste Argentino (IQUIBA-NEA), Universidad Nacional del Nordeste, Consejo Nacional de Investigaciones Científicas y Técnicas (UNNE-CONICET), Corrientes 3400, Argentina., Aguirre MV; Laboratorio de Investigaciones Bioquímicas de la Facultad de Medicina (LIBIM), Instituto de Química Básica y Aplicada del Nordeste Argentino (IQUIBA-NEA), Universidad Nacional del Nordeste, Consejo Nacional de Investigaciones Científicas y Técnicas (UNNE-CONICET), Corrientes 3400, Argentina., Balboa MA; Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), 47003 Valladolid, Spain.; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 28029 Madrid, Spain., Balsinde J; Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), 47003 Valladolid, Spain.; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 28029 Madrid, Spain., Rodríguez JP; Laboratorio de Investigaciones Bioquímicas de la Facultad de Medicina (LIBIM), Instituto de Química Básica y Aplicada del Nordeste Argentino (IQUIBA-NEA), Universidad Nacional del Nordeste, Consejo Nacional de Investigaciones Científicas y Técnicas (UNNE-CONICET), Corrientes 3400, Argentina. |
| Abstrakt: |
Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma (RCC). It is characterized by a high cell proliferation and the ability to store lipids. Previous studies have demonstrated the overexpression of enzymes associated with lipid metabolism, including stearoyl-CoA desaturase-1 (SCD-1), which increases the concentration of unsaturated fatty acids in tumor cells. In this work, we studied the expression of SCD-1 in primary ccRCC tumors, as well as in cell lines, to determine its influence on the tumor lipid composition and its role in cell proliferation. The lipidomic analyses of patient tumors showed that oleic acid (18:1 n -9) is one of the major fatty acids, and it is particularly abundant in the neutral lipid fraction of the tumor core. Using a ccRCC cell line model and in vitro-generated chemical hypoxia, we show that SCD-1 is highly upregulated (up to 200-fold), and this causes an increase in the cellular level of 18:1 n -9, which, in turn, accumulates in the neutral lipid fraction. The pharmacological inhibition of SCD-1 blocks 18:1 n -9 synthesis and compromises the proliferation. The addition of exogenous 18:1 n -9 to the cells reverses the effects of SCD-1 inhibition on cell proliferation. These data reinforce the role of SCD-1 as a possible therapeutic target. |
