FASN-TGF-ß1-PD-L1 axis contributes to the development of resistance to NK cell cytotoxicity of cisplatin-resistant lung cancer cells.
Biochim Biophys Acta Mol Cell Biol Lipids
; 1863(3): 313-322, 2018 Mar.
Article
em En
| MEDLINE
| ID: mdl-29306075
ABSTRACT
Cisplatin remains the most effective therapy for non-small cell lung cancer (NSCLC). We previously have found cisplatin-resistant lung cancer cells (A549CisR and H157CisR) were more resistant to natural killer (NK) cell-mediated cytotoxicity than parental cells. We also discovered that fatty acid synthase (FASN) levels in cisplatin-resistant cells were significantly higher than in parental cells. To reveal whether a link exists between the up-regulated FASN levels and higher resistance to NK cell cytotoxicity, we performed inhibition studies using a FASN inhibitor and applied the FASN knockdown approach. In both approaches, we found that the FASN inhibition/knockdown significantly increased the susceptibility of cisplatin-resistant cells to NK cell cytotoxicity. We further found such decreased susceptibility was associated with an increased programmed death receptor ligand (PD-L1) level in cisplatin-resistant cells. In mechanisms studies, TGF-ß1 was found to be the FASN downstream signaling molecule that was responsible for modulating the PD-L1 levels in cisplatin-resistant cells. Accordingly, TGF-ß1 inhibition resulted in significantly increased susceptibility of cisplatin-resistant cells to NK cell cytotoxicity. We suggest that the inhibition of FASN-TGFß1-PD-L1 axis may improve the efficacy of immunotherapy in treating cisplatin-resistant lung cancer.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
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Transdução de Sinais
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Cisplatino
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Resistencia a Medicamentos Antineoplásicos
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Fator de Crescimento Transformador beta1
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Ácido Graxo Sintase Tipo I
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Antígeno B7-H1
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Imunidade Celular
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Neoplasias Pulmonares
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Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta Mol Cell Biol Lipids
Ano de publicação:
2018
Tipo de documento:
Article