Journal article
A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability
AP Morel, C Ginestier, RM Pommier, O Cabaud, E Ruiz, J Wicinski, M Devouassoux-Shisheboran, V Combaret, P Finetti, C Chassot, C Pinatel, F Fauvet, P Saintigny, E Thomas, C Moyret-Lalle, J Lachuer, E Despras, JL Jauffret, F Bertucci, J Guitton Show all
Nature Medicine | NATURE PORTFOLIO | Published : 2017
DOI: 10.1038/nm.4323
Abstract
Chromosomal instability (CIN), a feature of most adult neoplasms from their early stages onward, is a driver of tumorigenesis. However, several malignancy subtypes, including some triple-negative breast cancers, display a paucity of genomic aberrations, thus suggesting that tumor development may occur in the absence of CIN. Here we show that the differentiation status of normal human mammary epithelial cells dictates cell behavior after an oncogenic event and predetermines the genetic routes toward malignancy. Whereas oncogene induction in differentiated cells induces massive DNA damage, mammary stem cells are resistant, owing to a preemptive program driven by the transcription factor ZEB1 a..
View full abstractGrants
Awarded by Ligue Nationale contre le Cancer
Awarded by Lyon Integrated Research Institute in Cancer (LYRIC)
Awarded by Institut National contre le Cancer
Awarded by Cancer-DGOS grant
Awarded by Marseille Integrated Research Institute in Cancer
Funding Acknowledgements
The authors thank I. Treilleux and G. Clapisson (Resource Biological Center) for providing tumor samples; N. Nazaret for sequencing analysis; P. Kannouche for providing help and laboratory space for the DNA-fiber spreading analysis; I. Iacono, S. Brejon, A. Pierrot, J. Perrossier and S. Croze for technical support; D. Negre (CIRI/EVIR) for providing the pWPIR-GFP lentiviral vector; C. Eaves (Terry Fox Laboratory) for providing cells; and M. Tommasino (IARC) for providing vectors. We thank the CRCM animal core facility for animal housing and the CRCM flow cytometry core (M.L. Thibullt) for technical assistance. We also thank B. Manship for critical reading of the manuscript. This work was supported by funding from the Ligue Nationale contre le Cancer (EL2011.LNCC/AP and EL2016.LNCC/AIP) and the Project National Cancer Association, Lyon Integrated Research Institute in Cancer (LYRIC, INCa 4664) to A.P. This work was additionally supported by funding from the Institut National contre le Cancer (project PLBio 2015-266) to P.S., the Institut National contre le Cancer (project PLBIO12-007) to E.D., a Cancer-DGOS grant (TRANSLA11-103) to E.C.-J. and the Marseille Integrated Research Institute in Cancer (INCa 6038) to D.B.