Artículo
The hypoxic microenvironment induces stearoyl-coa desaturase-1 overexpression and lipidomic profile changes in clear cell renal cell carcinoma
Melana Colavita, Juan Pablo
; Mignolli, Francesco
; Stoyanoff, Tania Romina
; Aguirre, María Victoria; Balboa, María A.; Balsinde Rodríguez, Jesús; Rodríguez, Juan Pablo
Fecha de publicación:
06/2021
Editorial:
MDPI
Revista:
Cancers
ISSN:
2072-6694
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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 (18:1n-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 18:1n-9, which, in turn, accumulates in the neutral lipid fraction. The pharmacological inhibition of SCD-1 blocks 18:1n-9 synthesis and compromises the proliferation. The addition of exogenous 18:1n-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.
Palabras clave:
HYPOXIA
,
KIDNEY
,
OLEIC ACID
,
SCD-1
,
TUMOR MICROENVIRONMENT
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(IBONE)
Articulos de INST.DE BOTANICA DEL NORDESTE (I)
Articulos de INST.DE BOTANICA DEL NORDESTE (I)
Articulos(IQUIBA-NEA)
Articulos de INSTITUTO DE QUIMICA BASICA Y APLICADA DEL NORDESTE ARGENTINO
Articulos de INSTITUTO DE QUIMICA BASICA Y APLICADA DEL NORDESTE ARGENTINO
Citación
Melana Colavita, Juan Pablo; Mignolli, Francesco; Stoyanoff, Tania Romina; Aguirre, María Victoria; Balboa, María A.; et al.; The hypoxic microenvironment induces stearoyl-coa desaturase-1 overexpression and lipidomic profile changes in clear cell renal cell carcinoma; MDPI; Cancers; 13; 12; 6-2021; 1-15
Compartir
Altmétricas