Oncotarget

Research Papers:

Human rpL3 plays a crucial role in cell response to nucleolar stress induced by 5-FU and L-OHP

Davide Esposito _, Elvira Crescenzi, Vinay Sagar, Fabrizio Loreni, Annapina Russo and Giulia Russo

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Oncotarget. 2014; 5:11737-11751. https://doi.org/10.18632/oncotarget.2591

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Abstract

Davide Esposito1,2, Elvira Crescenzi3, Vinay Sagar4, Fabrizio Loreni4, Annapina Russo5,*, Giulia Russo5,*

1Department of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”, Naples 80131, Italy

2Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA

3Institute of Experimental Endocrinology and Oncology-CNR, Naples 80131, Italy

4Department of Biology, University of Rome ‘Tor Vergata’, Rome 00133, Italy

5Department of Pharmacy, University of Naples “Federico II”, Naples 80131, Italy

*These authors contributed equally to this publication and share last authorship

Correspondence to:

Giulia Russo, e-mail: giulia.russo@unina.it

Annapina Russo, e-mail: annapina.russo@unina.it

Keywords: p21, ribosomal protein, 5-FU, Oxaliplatin, DNA repair

Received: August 18, 2014     Accepted: October 11, 2014     Published: November 28, 2014

ABSTRACT

Recent evidence showed that a variety of DNA damaging agents including 5-FU and L-OHP impairs ribosomal biogenesis activating a ribosomal stress pathway. Here, we demonstrate that in lung and colon cancer cell lines devoid of p53, the efficacy of 5-FU and L-OHP chemotherapy depends on rpL3 status. Specifically, we demonstrate that ribosomal stress induced by 5-FU and L-OHP is associated to up-regulation of rpL3 and its accumulation as ribosome-free form. We show that rpL3 participates in the cell response to chemotherapy acting as a critical regulator of cell cycle, apoptosis and DNA repair, by modulating p21 expression. Moreover, we demonstrate that rpL3 is able to control DNA repair also independently from p21 status of cell. It is noteworthy that silencing of rpL3 abolishes the cytotoxic effects of 5-FU and L-OH indicating that the loss of rpL3 makes chemotherapy drugs ineffective. Taking together our results shed light on 5-FU and L-OHP mechanism of action and contribute to more effective clinical use of these drugs in cancer therapy.


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