Inhibition of Stearoyl-CoA Desaturase 1 expression in human lung adenocarcinoma cells impairs tumorigenesis

Saturated (SFA) and monounsaturated (MUFA) fatty acids, the most abundant fatty acid species, have many divergent biological effects including the regulation of cell proliferation, programmed cell death and lipid-mediated cytotoxicity. Their distribution is regulated by Stearoyl-CoA Desaturases (SCD...

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Autores principales: Scaglia, Natalia, Igal, Rubén Ariel
Formato: Articulo
Lenguaje:Inglés
Publicado: 2008
Materias:
Ciencias Médicas
Akt pathway
Cell proliferation
Human cancer cells
Monounsaturated fatty acid synthesis
Tumor formation
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/84237
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-84237
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Akt pathway
Cell proliferation
Human cancer cells
Monounsaturated fatty acid synthesis
Tumor formation
spellingShingle Ciencias Médicas
Akt pathway
Cell proliferation
Human cancer cells
Monounsaturated fatty acid synthesis
Tumor formation
Scaglia, Natalia
Igal, Rubén Ariel
Inhibition of Stearoyl-CoA Desaturase 1 expression in human lung adenocarcinoma cells impairs tumorigenesis
topic_facet Ciencias Médicas
Akt pathway
Cell proliferation
Human cancer cells
Monounsaturated fatty acid synthesis
Tumor formation
description Saturated (SFA) and monounsaturated (MUFA) fatty acids, the most abundant fatty acid species, have many divergent biological effects including the 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 tissue 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 yet been firmly established. Here we report that the stable knockdown of SCD1 gene expression in A549 human lung adenocarcinoma cells decreased the ratio MUFA/SFA in total lipids and inhibited the incorporation of glucose into cell lipids. Cell proliferation and anchorage-independent growth were considerably decreased in SCD1-depleted cells, whereas the rate of apoptosis was elevated, with respect to control A549 cells. In addition, phosphorylation of Akt-Ser473 and GSK-3β-Ser9 was found notably impaired in SCD1-ablated A549 cells. Interestingly, the effects of SCD1 blockade on Akt activation, cancer cell growth and apoptosis could not be reversed by exogenously added oleic acid. Remarkably, the reduction 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 demonstrates that SCD1 activity regulates Akt activation and determines the rate of cell proliferation, survival and invasiveness in A549 cancer cells and shows, for the first time, that SCD1 is a key factor in the regulation of tumorigenesis <i>in vivo</i>.
format Articulo
Articulo
author Scaglia, Natalia
Igal, Rubén Ariel
author_facet Scaglia, Natalia
Igal, Rubén Ariel
author_sort Scaglia, Natalia
title Inhibition of Stearoyl-CoA Desaturase 1 expression in human lung adenocarcinoma cells impairs tumorigenesis
title_short Inhibition of Stearoyl-CoA Desaturase 1 expression in human lung adenocarcinoma cells impairs tumorigenesis
title_full Inhibition of Stearoyl-CoA Desaturase 1 expression in human lung adenocarcinoma cells impairs tumorigenesis
title_fullStr Inhibition of Stearoyl-CoA Desaturase 1 expression in human lung adenocarcinoma cells impairs tumorigenesis
title_full_unstemmed Inhibition of Stearoyl-CoA Desaturase 1 expression in human lung adenocarcinoma cells impairs tumorigenesis
title_sort inhibition of stearoyl-coa desaturase 1 expression in human lung adenocarcinoma cells impairs tumorigenesis
publishDate 2008
url http://sedici.unlp.edu.ar/handle/10915/84237
work_keys_str_mv AT scaglianatalia inhibitionofstearoylcoadesaturase1expressioninhumanlungadenocarcinomacellsimpairstumorigenesis
AT igalrubenariel inhibitionofstearoylcoadesaturase1expressioninhumanlungadenocarcinomacellsimpairstumorigenesis
bdutipo_str Repositorios
_version_ 1764820488516796419

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