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Article Dans Une Revue Oncotarget Année : 2016

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

Daniel Brown
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Jovana Kantar
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Michel Prudhomme
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Julie Pannequin

Résumé

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.
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hal-01431926 , version 1 (17-12-2020)

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Chris Planque, Fatemeh Rajabi, Fanny Grillet, Pascal Finetti, François Bertucci, et al.. Pregnane X-receptor promotes stem cell-mediated colon cancer relapse. Oncotarget, 2016, 7 (35), pp.56558-56573. ⟨10.18632/oncotarget.10646⟩. ⟨hal-01431926⟩
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