A novel bidirectional positive-feedback loop between Wnt-β-catenin and EGFR-ERK plays a role in context-specific modulation of epithelial tissue regeneration.

ABSTRACT: By operating as both a subunit of the cadherin complex and a key component of Wnt signalling, β-catenin acts as the lynchpin between cell-cell contact and transcriptional regulation of proliferation, coordinating epithelial tissue homeostasis and regeneration. The integration of multiple growth-regulatory inputs with β-catenin signalling has been observed in cancer-derived cells, yet the existence of pathway crosstalk in normal cells is unknown. Using a highly regenerative normal human epithelial culture system that displays contact inhibition, we demonstrate that the receptor tyrosine kinase (RTK)-driven MAPK and Wnt-β-catenin signalling axes form a bidirectional positive-feedback loop to drive cellular proliferation. We show that β-catenin both drives and is regulated by proliferative si

SUBMITTER: Georgopoulos NT 

PROVIDER: S-EPMC4077591 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature