Afficher la couverture 'Pregnane X-receptor promotes stem cell-mediated colon cancer relapse | Planque, Chris' en grand format
/5

0 avis

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

Archive ouverte

Planque, Chris | Rajabi, Fatemeh | Grillet, Fanny | Finetti, Pascal | Bertucci, François | Gironella, Meritxell | Lozano, Juan Jose | Beucher, Bertrand | Giraud, Julie | Garambois, Véronique | Vincent, Charles | Brown, Daniel | Caillo, Ludovic | Kantar, Jovana | Pèlegrin, André | Prudhomme, Michel | Ripoche, Jeremie | Bourgaux, Jean Francois | Ginestier, Christophe | Castells, Antoni | Hollande, Frédéric | Pannequin, Julie | Pascussi, Jean-Marc

Edité par CCSD ; Impact journals -

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.

Suggestions

Du même auteur

Autocrine Secretion of Progastrin Promotes the Survival and Self-Renewal of Colon Cancer Stem-like Cells

Archive ouverte | Giraud, Julie | CCSD

International audience. Subpopulations of cancer stem-like cells (CSC) are thought to drive tumor progression and posttreatment recurrence in multiple solid tumors. However, the mechanisms that maintain stable propo...

Characterization of a novel PXR isoform with potential dominant-negative properties

Archive ouverte | Breuker, Cyril | CCSD

International audience. BACKGROUND & AIMS: The nuclear Pregnane X Receptor (PXR, NR1I2) plays a pivotal role in xenobiotic metabolism. Here, we sought to characterize a new PXR isoform (hereafter called small PXR or...

Tight Junction Protein Claudin-2 Promotes Self-Renewal of Human Colorectal Cancer Stem-like Cells

Archive ouverte | Paquet-Fifield, S. | CCSD

International audience. Posttreatment recurrence of colorectal cancer, the third most lethal cancer worldwide, is often driven by a subpopulation of cancer stem cells (CSC). The tight junction (TJ) protein claudin-2...

Chargement des enrichissements...