E-cadherin: A potential biomarker of colorectal cancer prognosis

Abstract

Colorectal cancer (CRC) is a common and lethal disease. It is the third most common type of cancer in the world, behind lung and breast cancer, with almost 1.4 million new cases diagnosed in 2012. The risk of developing CRC is influenced by environmental and genetic factors. Adenocarcinomas comprise the vast majority (98%) of CRCs. A patient's likelihood of survival is associated with the tumor stage at the time of diagnosis. With regular screening, CRC can be identified early, when treatment is the most effective. However, CRC is typically asymptomatic until the advanced stages. The combination of the absence of symptoms and current screening methodology results in a significant number of patients being diagnosed in advanced stages. The purpose of the present review is to discuss and summarize the biomarkers linked to CRC progression, particularly the controversial E-cadherin, which is a calcium-dependent cell-cell adhesion molecule involved in the mesenchymal-epithelial transition.

Keywords: E-cadherin protein; biomarkers; colorectal cancer.

Figure 1.

Interaction of the E-cadherin-catenin complex. The cadherin adhesion system is linked to the actin-based cytoskeleton via catenins. The figure illustrates protein interactions between different catenin pools, E cadherin and p120-catenin (p120), regulating the dynamic assembly and disassembly of the cadherin-catenin complex and its function in signal transduction. β/PL, β-catenin or plakoglobin; α, α-catenin; P-Tyr, tyrosine phosphorylation; APC, adenomatosis polyposis coli-Wnt signaling pathway regulator.

Figure 2.

Operating mode of the E-cadherin-catenin complex in tumor metastasis. Stimulation of EGFR and c-Met receptors led to the translocation of ß-catenin into the cytosolic pool where it can be degraded. If the Wnt1 pathway is activated at the same time as the other two pathways, the degradation of ß-catenin is inhibited and it is translocated to the nucleus to combine with LEF/TCF, causing transcription of the cyclin D1 gene and downregulation of the CDH1 gene. Reversal by way of contact inhibition is poorly understood. E-CAD, E-cadherin; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; HGF, hepatocyte growth factor; c-Met, hepatocyte growth factor receptor; GAP, GTPase activating protein; β, β-catenin; α, α-catenin; IQGAP1, IQ motif-containing GTPase activating protein 1; GDP, guanosine diphosphate; GSK3β, glycogen synthase kinase 3β; APC, adenomatosis polyposis coli Wnt signaling pathway regulator; P, phosphorylation group; Dsh, disheveled; LEF/TCF, lymphoid enhancer factor/T-cell factor family of transcription factors; CDH1, cadherin 1 (E-cadherin gene); p27Kip1, cyclin-dependent kinase inhibitor 1B.

Figure 3.

Schematic representation of E-cadherin protein. The protein contains ECs, a JMD and a CBD, together with cleavage sites for MMPs and γ-secretase, and a binding domain for PS1. EC, extracellular domain; JMD, juxtamembrane domain; CBD, catenin-binding domain; MMP, matrix metalloproteinase; PS1, presenilin-1; TM, transmembrane domain.