Pregnane X-receptor promotes stem cell-mediated colon cancer relapse
| Autor: | J. Ripoche, Daniel Brown, Fatemeh Rajabi, Véronique Garambois, Bertrand Beucher, Antoni Castells, Frédéric Hollande, Meritxell Gironella, Pascal Finetti, Julie Giraud, Jovana Kantar, André Pèlegrin, Charles Vincent, Julie Pannequin, Jean-Marc Pascussi, Ludovic Caillo, Jean-François Bourgaux, Michel Prudhomme, François Bertucci, Juan José Lozano, Christophe Ginestier, Fanny Grillet, Chris Planque |
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| Přispěvatelé: | Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Institut d'Investigaciones Biomèdiques August Pi i Sunye (IDIBAPS), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Melbourne, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Ginestier, Christophe, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Receptors Steroid Colorectal cancer Cohort Studies Mice Medicine Pregnane X receptor Mice Inbred BALB C Pregnane X Receptor Prognosis 3. Good health Oncology Colonic Neoplasms Neoplastic Stem Cells [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Female Stem cell Research Paper cancer stem cell PXR Mice Nude [SDV.CAN]Life Sciences [q-bio]/Cancer colorectal cancer Antineoplastic Agents [SDV.BC]Life Sciences [q-bio]/Cellular Biology digestive system Aldehyde Dehydrogenase 1 Family Disease-Free Survival 03 medical and health sciences Breast cancer [SDV.CAN] Life Sciences [q-bio]/Cancer Side population Cancer stem cell [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Spheroids Cellular Biomarkers Tumor Gene silencing Animals Humans [SDV.BC] Life Sciences [q-bio]/Cellular Biology Aged business.industry Retinal Dehydrogenase [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology Aldehyde Dehydrogenase medicine.disease tumor recurrence [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology digestive system diseases 030104 developmental biology Nuclear receptor Drug Resistance Neoplasm Cancer research Neoplasm Recurrence Local business Neoplasm Transplantation |
| Zdroj: | Oncotarget Oncotarget, Impact journals, 2016, 7 (35), pp.56558-56573. ⟨10.18632/oncotarget.10646⟩ Oncotarget, 2016, 7 (35), pp.56558-56573. ⟨10.18632/oncotarget.10646⟩ |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.10646⟩ |
| Popis: | International audience; 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 increased the chemo-sensitivity of human colon CSCs, reduced their self-renewal and tumor-initiating potential, and drastically delayed tumor recurrence in mice following chemotherapy. This study uncovers PXR as a key factor for CSC self-renewal and chemoresistance and targeting PXR thus represents a promising strategy to minimize colorectal cancer relapse by selectively sensitizing CSCs to chemotherapy. |
| Databáze: | OpenAIRE |
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