The cellular prion protein controls the mesenchymal-like molecular subtype and predicts disease outcome in colorectal cancer

EBioMedicine
Delphine Le CorreSophie Mouillet-Richard

Abstract

Comprehensive transcriptomic analyses have shown that colorectal cancer (CRC) is heterogeneous and have led to the definition of molecular subtypes among which the stem-cell, mesenchymal-like group is associated with poor prognosis. The molecular pathways orchestrating the emergence of this subtype are incompletely understood. In line with the contribution of the cellular prion protein PrPC to stemness, we hypothesize that deregulation of this protein could lead to a stem-cell, mesenchymal-like phenotype in CRC. We assessed the distribution of the PrPC-encoding PRNP mRNA in two large CRC cohorts according to molecular classification and its association with patient survival. We developed cell-based assays to explore the impact of gain and loss of PrPC function on markers of the mesenchymal subtype and to delineate the signalling pathways recruited by PrPC. We measured soluble PrPC in the plasmas of 325 patients with metastatic CRC and probed associations with disease outcome. We found that PRNP gene expression is enriched in tumours of the mesenchymal subtype and is associated with poor survival. Our in vitro analyses revealed that PrPC controls the expression of genes that specify the mesenchymal subtype through the recruitmen...Continue Reading

Citations

Sep 26, 2019·Journal of Neuropathology and Experimental Neurology·Aušrinė AreškevičiūtėEva L Lund
Oct 18, 2019·International Journal of Molecular Sciences·Larisa RyskalinFrancesco Fornai
Dec 6, 2020·International Journal of Molecular Sciences·Gyeongyun Go, Sang Hun Lee
Nov 1, 2020·Cancers·Sophie Mouillet-Richard, Pierre Laurent-Puig
May 8, 2021·Biological Reviews of the Cambridge Philosophical Society·Gerold Schmitt-UlmsSepehr Ehsani
May 28, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Guanglin CuiRasmus Goll
Jul 13, 2021·Oncoimmunology·Alexandre GhaziSophie Mouillet-Richard
Jul 22, 2021·Cell Reports·Sebastian M DieterHanno Glimm

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Datasets Mentioned

BETA
GSE39582

Methods Mentioned

BETA
Infrared Imaging
PCR
nuclear translocation

Clinical Trials Mentioned

NCT00952029

Software Mentioned

GSEA
R package
SDS

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