Serum Levels of the Cytokine TWEAK Are Associated with Metabolic Status in Patients with Prostate Cancer and Modulate Cancer Cell Lipid Metabolism In Vitro

Cancers

Antonio Altuna-Coy¹  Matilde R. Chacón¹  Xavier Ruiz-Plazas¹  Marta Alves-Santiago¹  José Segarra-Tomás¹ 

[1] Disease Biomarkers and Molecular Mechanisms Group, IISPV, Joan XXIII University Hospital, Universitat Rovira i Virgili, 43007 Tarragona, Spain;

关键词: TWEAK;    prostate cancer;    lipid metabolism;    Fn14;   

DOI  :  10.3390/cancers13184688

来源: DOAJ

【 摘 要 】

Soluble TWEAK (sTWEAK) has been proposed as a prognostic biomarker of prostate cancer (PCa). We found that reduced serum levels of sTWEAK, together with higher levels of prostate-specific antigen and a higher HOMA-IR index, are independent predictors of PCa. We also showed that sTWEAK stimulus failed to alter the expression of glucose transporter genes (SLC2A4 and SLC2A1), but significantly reduced the expression of glucose metabolism-related genes (PFK, HK1 and PDK4) in PCa cells. The sTWEAK stimulation of PC-3 cells significantly increased the expression of the genes related to lipogenesis (ACACA and FASN), lipolysis (CPT1A and PNPLA2), lipid transport (FABP4 and CD36) and lipid regulation (SREBP-1 and PPARG) and increased the lipid uptake. Silencing the TWEAK receptor (Fn14) in PC-3 cells confirmed the observed lipid metabolic effects, as shown by the downregulation of ACACA, FASN, CPT1A, PNPLA2, FABP4, CD36, SREBP-1 and PPARG expression, which was paralleled by a reduction of FASN, CPT1A and FABP4 protein expression. Specific-signaling inhibitor assays show that ERK1/2 and AKT (ser473) phosphorylation can regulate lipid metabolism-related genes in PCa cells, pointing to the AKT locus as a possible target for PCa. Overall, our data support sTWEAK/Fn14 axis as a potential therapeutic target for PCa.

【 授权许可】

Unknown