Prognostic value of the PrP^C-ILK-IDO1 axis in the mesenchymal colorectal cancer subtype.

ABSTRACT: The CMS4 mesenchymal subtype of colorectal cancer (CRC) is associated with poor prognosis and resistance to treatment. The cellular prion protein PrP^C is overexpressed in CMS4 tumors and controls the expression of a panel of CMS4-specific genes in CRC cell lines. Here, we sought to investigate PrP^C downstream pathways that may underlie its role in CMS4 CRC. By combining gene set enrichment analyses and gain and loss of function approaches in CRC cell lines, we identify the integrin-linked kinase ILK as a proximal effector of PrP^C that mediates its control on the CMS4 phenotype. We further leveraged three independent large CRC cohorts to assess correlations in gene expression pattern with patient outcomes and found that ILK is overexpressed in CMS4 mesenchym

SUBMITTER: Ghazi A 

PROVIDER: S-EPMC8244775 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature