Transcriptomal profiling of the cellular response to DNA damage mediated by Slug (Snai2)

British Journal of Cancer
María Pérez-CaroIsidro Sánchez-García

Abstract

Snai2-deficient cells are radiosensitive to DNA damage. The function of Snai2 in response to DNA damage seems to be critical for its function in normal development and cancer. Here, we applied a functional genomics approach that combined gene-expression profiling and computational molecular network analysis to obtain global dissection of the Snai2-dependent transcriptional response to DNA damage in primary mouse embryonic fibroblasts (MEFs), which undergo p53-dependent growth arrest in response to DNA damage. Although examination of the response showed that overall expression of p53 target gene expression patterns was similarly altered in both control and Snai2-deficient cells, we have identified and validated candidate Snai2 target genes linked to Snai2 gene function in response to DNA damage. This work defines for the first time the effect of Snai2 on p53 target genes in cells undergoing growth arrest, elucidates the Snai2-dependent molecular network induced by DNA damage, points to novel putative Snai2 targets, and suggest a mechanistic model, which has implications for cancer management.

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Citations

Nov 9, 2014·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Xinqiong HuangXiang Chen
Jan 23, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Chiara RaggiSnorri S Thorgeirsson
May 28, 2010·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Modjtaba Emadi BaygiWolfgang A Schulz
Feb 19, 2011·Critical Reviews in Toxicology·Kamyar GhabiliMohammadali M Shoja
Dec 20, 2012·Cellular Oncology (Dordrecht)·Chiara ArientiWainer Zoli
Mar 17, 2018·Experimental and Therapeutic Medicine·Hongxia YangShudong Yu
Dec 22, 2012·The Journal of Clinical Investigation·Michael A AugelloKaren E Knudsen
Jun 10, 2016·International Journal of Oncology·Fangfang JiangDongsheng Yu
Sep 17, 2013·The American Journal of Pathology·Gianluca StorciMassimiliano Bonafé

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Methods Mentioned

BETA
FCS
FACS
electrophoresis
PCR
dissection

Software Mentioned

SDS
Ingenuity
Ingenuity Pathways Analysis
GenePix

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