Journal article

Pregnane X-receptor promotes stem cell-mediated colon cancer relapse

Chris Planque, Fatemeh Rajabi, Fanny Grillet, Pascal Finetti, Francois Bertucci, Meritxell Gironella, Juan Jose Lozano, Bertrand Beucher, Julie Giraud, Veronique Garambois, Charles Vincent, Daniel Brown, Ludovic Caillo, Jovana Kantar, Andre Pelegrin, Michel Prudhomme, Jeremie Ripoche, Jean Francois Bourgaux, Christophe Ginestier, Antoni Castells Show all

ONCOTARGET | IMPACT JOURNALS LLC | Published : 2016

Abstract

Colorectal cancer lethality usually results from post-treatment relapse in the majority of stage II-IV patients, due to the enhanced resistance of Cancer Stem Cells (CSCs). Here, we show that the nuclear receptor Pregnane X Receptor (PXR, NR1I2), behaves as a key driver of CSC-mediated tumor recurrence. First, PXR is specifically expressed in CSCs, where it drives the expression of genes involved in self-renewal and chemoresistance. Clinically, high levels of PXR correlate with poor recurrence-free survival in a cohort of >200 stage II/III colorectal cancer patients treated with chemotherapy, for whom finding biomarkers of treatment outcome is an urgent clinical need. shRNA silencing of PXR ..

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University of Melbourne Researchers

Grants

Awarded by Association pour la Recherche contre le Cancer


Awarded by Ligue regionale contre le cancer (Herault)


Awarded by National Health and Medical Research Council of Australia


Awarded by Fundacion Cientifica de la Asociacion Espanola contra el Cancer


Funding Acknowledgements

We thank P. Crespy for his technical expertise and lab management, C. Duperray (IRBM, Montpellier) and M. Boyer (IGMM, Montpellier) from the Montpellier RIO Imaging platform for flow cytometry experiments, and M. Asari for her help in figure design. This work was supported by Grants from the Labex EpiGenMed and Universite de Montpellier (F.R), Association pour la Recherche contre le Cancer (#16922 and SFI20121205749), Ligue regionale contre le cancer (Herault, 6F11728PMBZ), the National Health and Medical Research Council of Australia (##1049561) and from Fundacion Cientifica de la Asociacion Espanola contra el Cancer (GCB13131592CAST).