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

C Planque; F Rajabi; F Grillet; P Finetti; F Bertucci; M Gironella; JJ Lozano; B Beucher; J Giraud; V Garambois; C Vincent; D Brown; L Caillo; J Kantar; A Pelegrin; M Prudhomme; J Ripoche; JF Bourgaux; C Ginestier; A Castells; F Hollande; J Pannequin; JM Pascussi

Journal article

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

C Planque, F Rajabi, F Grillet, P Finetti, F Bertucci, M Gironella, JJ Lozano, B Beucher, J Giraud, V Garambois, C Vincent, D Brown, L Caillo, J Kantar, A Pelegrin, M Prudhomme, J Ripoche, JF Bourgaux, C Ginestier, A Castells Show all

Oncotarget | IMPACT JOURNALS LLC | Published : 2016

DOI: 10.18632/oncotarget.10646

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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

Daniel V Brown Author

Frederic Hollande Author

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Grants

Awarded by National Health and Medical Research Council

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).