Lactate Increases Renal Cell Carcinoma Aggressiveness through Sirtuin 1-Dependent Epithelial Mesenchymal Transition Axis Regulation.

ABSTRACT: Renal cell carcinoma (RCC) displays a glycolytic phenotype (Warburg effect). Increased lactate production, impacting on tumor biology and microenvironment modulation, has been implicated in epigenetic mechanisms' regulation, leading to histone deacetylases inhibition. Thus, in-depth knowledge of lactate's impact on epigenome regulation of highly glycolytic tumors might allow for new therapeutic strategies. Herein, we investigated how extracellular lactate affected sirtuin 1 activity, a class III histone deacetylase (sirtuins, SIRTs) in RCC. In vitro and in vivo interactions between lactate and SIRT1 in RCC were investigated in normal kidney and RCC cell lines. Finally, SIRT1 and N-cadherin immunoexpression was assessed in human RCC and normal renal tissues. Lactate inhibited SIRT1 expressi

SUBMITTER: Miranda-Goncalves V 

PROVIDER: S-EPMC7226526 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature