A β-Catenin-TCF-Sensitive Locus Control Region Mediates GUCY2C Ligand Loss in Colorectal Cancer.

ABSTRACT:

Background & aims

Sporadic colorectal cancers arise from initiating mutations in APC, producing oncogenic β-catenin/TCF-dependent transcriptional reprogramming. Similarly, the tumor suppressor axis regulated by the intestinal epithelial receptor GUCY2C is among the earliest pathways silenced in tumorigenesis. Retention of the receptor, but loss of its paracrine ligands, guanylin and uroguanylin, is an evolutionarily conserved feature of colorectal tumors, arising in the earliest dysplastic lesions. Here, we examined a mechanism of GUCY2C ligand transcriptional silencing by β-catenin/TCF signaling.

Methods

We performed RNA sequencing analysis of 4 unique conditional human colon cancer cell models of β-catenin/TCF signaling to map the core Wnt-transcriptional program. We then

SUBMITTER: Rappaport JA 

PROVIDER: S-EPMC9073733 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature