The ribosomal protein S6 in renal cell carcinoma: functional relevance and potential as biomarker.

ABSTRACT: Inhibitors of the mTOR pathway, such as everolimus, are promising compounds to treat patients with renal cell carcinomas (RCCs). However, the precise mechanisms of action are far from clear, and biomarkers predicting the response to mTOR inhibitors are still missing. Here, we provide evidence that in RCCs the rpS6 protein is the major mediator of anti-tumoral effects exerted by everolimus. Inhibition of mTOR signaling results in substantially decreased clonogenicity and proliferation of RCC cells, but did not significantly induce apoptosis. Everolimus effectively blocked protein biosynthesis both in vitro and in a novel ex vivo tissue slice model using fresh vital human RCC tissue. Compared to other components of the mTOR pathway, phosphorylation of rpS6 was most effectively downregulated

SUBMITTER: Knoll M 

PROVIDER: S-EPMC4808008 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature