Related Experiment Video

Updated: Jul 2, 2025

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells
08:54

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells

Published on: July 20, 2014

14.1K

E-cadherin loss drives diffuse-type gastric tumorigenesis via EZH2-mediated reprogramming

Gengyi Zou1, Yuanjian Huang1,2, Shengzhe Zhang1

  • 1Division of Radiation Oncology, Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

The Journal of Experimental Medicine
|February 27, 2024
PubMed

Insights

Diffuse-type gastric adenocarcinoma (DGAC) subtypes were identified, with CDH1 loss linked to distinct molecular features and immune evasion. This discovery offers new avenues for personalized treatment strategies in gastric cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Diffuse-type gastric adenocarcinoma (DGAC) is aggressive and treatment-resistant.
  • The role of CDH1/E-cadherin inactivation in sporadic DGAC is not well understood.
  • Hereditary DGAC is associated with CDH1 mutations.

Purpose of the Study:

  • To investigate the role of CDH1 inactivation in sporadic DGAC.
  • To identify molecular subtypes of DGAC.
  • To explore therapeutic targets for DGAC.

Main Methods:

  • Single-cell transcriptomic analysis of malignant ascites.
  • Genetically engineered murine gastric organoid models.
  • Analysis of CDH1 and EZH2 expression and function.

Main Results:

  • Two DGAC subtypes identified: DGAC1 (CDH1 loss) and DGAC2 (immune-evasive).
  • DGAC1 exhibits unique molecular signatures and abundant exhausted T cells.
  • Cdh1 knockout accelerates gastric tumorigenesis and immune evasion in murine models.
  • EZH2 identified as a mediator in CDH1 loss-associated DGAC.

Conclusions:

  • DGAC is molecularly diverse, with CDH1 inactivation defining a distinct subtype.
  • CDH1 loss promotes tumorigenesis and immune evasion in DGAC.
  • Targeting EZH2 or leveraging CDH1 status may enable personalized DGAC treatments.

More Related Videos

Induction and Analysis of Epithelial to Mesenchymal Transition10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

35.8K
Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies07:47

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies

Published on: September 15, 2023

1.5K

Related Concept Videos

Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
3.0K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
Structure of Cadherins01:25

Structure of Cadherins

The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This...
3.3K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.5K