Diacylglycerol Metabolism and Signaling Is a Driving Force Underlying FASN Inhibitor Sensitivity in Cancer Cells.
ACS Chem Biol
; 10(7): 1616-23, 2015 Jul 17.
Article
en En
| MEDLINE
| ID: mdl-25871544
ABSTRACT
Fatty acid synthase (FASN) generates the de novo source of lipids for cell proliferation and is a promising cancer therapy target. Development of FASN inhibitors, however, necessitates a better understanding of sensitive and resistant cancer types to optimize patient treatment. Indeed, testing the cytotoxic effects of FASN inhibition across human cancer cells revealed diverse sensitivities. We show here that metabolic incorporation of glucose into specific complex lipid species strongly predicts FASN inhibitor sensitivity. We also show that the levels of one of these lipid classes, protein kinase C (PKC) stimulator diacylglycerols, are lowered upon FASN inhibitor treatment in sensitive compared to resistant cells and that PKC activators and inhibitors rescue cell death in sensitive cells and sensitize resistant cells, respectively. Our findings not only reveal a biomarker for predicting FASN sensitivity in cancer cells but also a put forth a heretofore unrecognized mechanism underlying the anticancer effects of FASN inhibitors.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Diglicéridos
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Inhibidores Enzimáticos
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Ácido Graso Sintasas
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Neoplasias
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Antineoplásicos
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2015
Tipo del documento:
Article