E-cadherin Beyond Structure: A Signaling Hub in Colon Homeostasis and Disease

Abstract

E-cadherin is the core component of epithelial adherens junctions, essential for tissue development, differentiation, and maintenance. It is also fundamental for tissue barrier formation, a critical function of epithelial tissues. The colon or large intestine is lined by an epithelial monolayer that encompasses an E-cadherin-dependent barrier, critical for the homeostasis of the organ. Compromised barriers of the colonic epithelium lead to inflammation, fibrosis, and are commonly observed in colorectal cancer. In addition to its architectural role, E-cadherin is also considered a tumor suppressor in the colon, primarily a result of its opposing function to Wnt signaling, the predominant driver of colon tumorigenesis. Beyond these well-established traditional roles, several studies have portrayed an evolving role of E-cadherin as a signaling epicenter that regulates cell behavior in response to intra- and extra-cellular cues. Intriguingly, these recent findings also reveal tumor-promoting functions of E-cadherin in colon tumorigenesis and new interacting partners, opening future avenues of investigation. In this Review, we focus on these emerging aspects of E-cadherin signaling, and we discuss their implications in colon biology and disease.

Keywords: CDH1; adherens junctions; cadherin; catenin; colon crypt; colorectal cancer; epithelial; inflammatory bowel disease; microbiome.

Figure 1

A summary of the pro- and anti-tumorigenic signaling mediated by E-cadherin-based Adherens Junctions AJ complexes that has been described in colon cells and tissues. (A) Shades of green/blue depict tumor-suppressing components and functions, whereas (B) shades of red represent the tumor-promoting ones described in the text. T-arrows represent inhibition of molecules or pro-tumorigenic signaling processes; straight arrows represent activation of molecules or pro-tumorigenic signaling processes. β-cat: β-catenin; p120: p120 catenin; RISC: RNA-induced silencing complex.

Figure 2

A summary of the E-cadherin-mediated signaling and interactions involved in Inflammatory Bowel Disease IBD. T-arrows represent inhibition of molecules or processes; straight arrows represent activation of molecules or processes. β-cat: β-catenin; p120: p120 catenin.

Figure 3

A schematic summarizing interactions of E-cadherin with the colon microbiome. Straight arrows represent activation of molecules or processes β-cat: β-catenin; p120: p120 catenin.