Overview on the Role of E-Cadherin in Gastric Cancer: Dysregulation and Clinical Implications

Abstract

Gastric cancer is the fifth most common cancer and the third most common cause of cancer death all over the world. E-cadherin encoded by human CDH1 gene plays important roles in tumorigenesis as well as in tumor progression, invasion and metastasis. Full-length E-cadhrin tethered on the cell membrane mainly mediates adherens junctions between cells and is involved in maintaining the normal structure of epithelial tissues. After proteolysis, the extracellular fragment of the full-length E-cadhein is released into the extracellular environment and the blood, which is called soluble E-cadherin (sE-cadherin). sE-cadherin promots invasion and metastasis as a paracrine/autocrine signaling molecule in the progression of various types of cancer including gastric cancer. This review mainly summarizes the dysregulation of E-cadherin and the regulatory roles in the progression, invasion, metastasis, and drug-resistance, as well as its clinical applications in diagnosis, prognosis, and therapeutics of gastric cancer.

Two distinct phenotypes of immunologically hot gastric cancer subtypes

“…In this manner, E-cadherin restricts cell migration and suppresses metastasis [ 18 ]. In gastric cancer, loss of function of adhesive factors such as CDH1 is reported to contribute to tumor progression and metastasis [ 19 ]. Thus, the fact that the expression of CDH1, the E-cadherin gene, was identified as a factor strongly associated with the poor prognosis of patients in the Hot 1 group ( Fig.…”

“…On the other hand, there is also a report that E-cadherin expression facilitates tumor growth and metastasis formation in breast cancer [ 20 ], which might be involved in the progression and poor prognosis of Hot 1 tumors, but not necessarily other gastric cancer subtypes or other cancer entities. Currently, several E-cadherin activators that restore their expression are expected to inhibit EMT and metastasis [ 19 ]. However, the pro-metastatic or anti-metastatic function of E-cadherin is likely to be highly context-dependent.…”

Bacterial Involvement in Progression and Metastasis of Colorectal Neoplasia

“…E-cadherins are transmembrane glycoproteins that mediate intercellular adhesion and signaling [ 69 ]. Several epithelial tumors, including adenocarcinoma of the stomach involve diminished E-cadherin function due to pathogenic mutations [ 70 ]. Cellular adhesion molecules such as E-cadherin and β-catenin maintain epithelial tumor cell connections in the primary tumor.…”

Development and Application of Patient-Derived Cancer Organoidsin Clinical Management of Gastrointestinal Cancer: A State-of-the-Art Review

“…Cadherin 1 (CDH1), Ras homologue family member A (RHOA), and RhoGTPase Activating Protein (ARHGAP) can be found in GS-GC (38). E-Cadherin encoded by CDH1 is a vital molecule of epithelial cell homeostasis and plays an important role in intercellular adhesion (60,61). While RhoA is a member of small GTPases of the Rho family, which is a molecular switch that cycles between a GTPbound active form and a GAP inactive form, and RhoA activation plays a crucial role in actin cytoskeletal rearrangement (62).…”