RPS17 can act as a tumor suppressive ribosomal protein in human cell lines

Abstract

Certain ribosomal proteins (RPs) function as tumor suppressors. For example, RPL5 and RPL11 suppress oncogenesis by binding to MDM2 and thereby up-regulating p53, a mechanism referred to as the RP-MDM2-p53 cascade. However, whether other cancer-associated ribosomal proteins actually function as tumor suppressors has remained largely unclear. Previously, we showed that siRNA-mediated silencing of RPS17, in combination with expression of HPV16 E7 and activated KRAS G12V, transformed normal human fibroblasts. Here, we expanded our study to perform a functional analysis of RPS17 as a tumor suppressor. We first demonstrate that shRNA-mediated RPS17 silencing also promotes oncogenic transformation of human fibroblasts in vitro and in vivo. Conversely, its overexpression inhibits the soft agar colony formation of colon cancer-derived HCT116 cells in a p53-dependent manner. RPS17 weakly interacts with MDM2. However, unlike RPL5 and RPL11, overexpression of RPS17 does not increase p53 levels and its silencing induces p53, suggesting that the RP-MDM2-p53 cascade might not be a major pathway for its tumor-suppressive function. We further show that RPS17 binds to nucleophosmin and modulates its nuclear localization. Although the detailed molecular mechanisms underlying the tumor-suppressive function of RPS17 remain to be elucidated, this study provides evidence that RPS17 can function as a tumor suppressor.