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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-MDM...2-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.続きを見る
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