NONO and RALY proteins are required for YB-1 oxaliplatin induced resistance in colon adenocarcinoma cell lines

Molecular Cancer

Research

Chantal Garand¹  Serges P Tsofack²  Michel Lebel²  Donald Chow³  Hongwei H Yin³  Meraj Aziz³  Chris Sereduk³  David Guay⁴ 

[1] Centre de Recherche en Cancérologie de l'Université Laval, Hôpital Hôtel-Dieu de Québec, 9 McMahon St, G1R 2J6, Québec, Canada;Centre de Recherche en Cancérologie de l'Université Laval, Hôpital Hôtel-Dieu de Québec, 9 McMahon St, G1R 2J6, Québec, Canada;Quebec-Clinical Research Organization in Cancer consortium, (Q-CROC), Canada;Clinical Translational Research Division, Translational Genomics Research Institute, 13208 E Shea Blvd, 85259, AZ, USA;Feldan Bio Inc., 4975 Rideau, Suite 100, G2E 5H5, Québec, Canada;

关键词: Oxaliplatin;    HT29 Cell;    SW480 Cell;    Colorectal Cancer Cell;    Colorectal Cancer Cell Line;   

DOI  :  10.1186/1476-4598-10-145

 received in 2011-07-26, accepted in 2011-11-25,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundYB-1 is a multifunctional protein that affects transcription, splicing, and translation. Overexpression of YB-1 in breast cancers causes cisplatin resistance. Recent data have shown that YB-1 is also overexpress in colorectal cancer. In this study, we tested the hypothesis that YB-1 also confers oxaliplatin resistance in colorectal adenocarcinomas.ResultsWe show for the first time that transfection of YB-1 cDNA confers oxaliplatin resistance in two colorectal cancer cell lines (SW480 and HT29 cell lines). Furthermore, we identified by mass spectrometry analyses important YB-1 interactors required for such oxaliplatin resistance in these colorectal cancer cell lines. A tagged YB-1 construct was used to identify proteins interacting directly to YB-1 in such cells. We then focused on proteins that are potentially involved in colorectal cancer progression based on the Oncomine microarray database. Genes encoding for these YB-1 interactors were also examined in the public NCBI comparative genomic hybridization database to determine whether these genes are localized to regions of chromosomes rearranged in colorectal cancer tissues. From these analyses, we obtained a list of proteins interacting with YB-1 and potentially involved in oxaliplatin resistance. Oxaliplatin dose response curves of SW480 and HT29 colorectal cancer cell lines transfected with several siRNAs corresponding to each of these YB-1 interactors were obtained to identify proteins significantly affecting oxaliplatin sensitivity upon gene silencing. Only the depletion of either NONO or RALY sensitized both colorectal cancer cell lines to oxaliplatin. Furthermore, depletion of NONO or RALY sensitized otherwise oxaliplatin resistant overexpressing YB-1 SW480 or HT29 cells.ConclusionThese results suggest knocking down NONO or RALY significant counteracts oxaliplatin resistance in colorectal cancers overexpressing the YB-1 protein.

【 授权许可】

Unknown   
© Tsofack et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.