| Added by | celine.gongora |
|---|---|
| Group name | EquipeCG |
| Item Type | Journal Article |
| Title | Pregnane X-receptor promotes stem cell-mediated colon cancer relapse |
| Creator | Planque et al. |
| Author | Chris Planque |
| Author | Fatemeh Rajabi |
| Author | Fanny Grillet |
| Author | Pascal Finetti |
| Author | François Bertucci |
| Author | Meritxell Gironella |
| Author | Juan José Lozano |
| Author | Bertrand Beucher |
| Author | Julie Giraud |
| Author | Véronique Garambois |
| Author | Charles Vincent |
| Author | Daniel Brown |
| Author | Ludovic Caillo |
| Author | Jovana Kantar |
| Author | Michel Prudhomme |
| Author | Jérémie Ripoche |
| Author | Jean François Bourgaux |
| Author | Christophe Ginestier |
| Author | Antoni Castells |
| Author | Frédéric Hollande |
| Author | Julie Pannequin |
| Author | Jean Marc Pascussi |
| 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 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. |
| Publication | Oncotarget |
| Volume | 7 |
| Issue | 35 |
| Pages | 56558-56573 |
| Date | Aug 30, 2016 |
| Journal Abbr | Oncotarget |
| Language | eng |
| DOI | 10.18632/oncotarget.10646 |
| ISSN | 1949-2553 |
| Library Catalog | PubMed |
| Extra | PMID: 27448961 PMCID: PMC5302934 |
| Tags | Aged, Aldehyde Dehydrogenase, Animals, Antineoplastic Agents, arc, Biomarkers, Tumor, cancer stem cell, Cohort Studies, Colonic Neoplasms, colorectal cancer, Disease-Free Survival, Drug Resistance, Neoplasm, Female, Humans, Labex epigenmed, ligue, Male, Mice, Mice, Inbred BALB C, Mice, Nude, MRI, Neoplasm Recurrence, Local, Neoplasm Transplantation, Neoplastic Stem Cells, original, phd, Pregnane X Receptor, Prognosis, PXR, Receptors, Steroid, Spheroids, Cellular, tumor recurrence |
| Date Added | 2019/05/22 - 08:29:49 |
| Date Modified | 2019/10/24 - 17:26:28 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
Institut de Recherche en Cancérologie de
