Related Experiment Video
Updated: Sep 17, 2025
10:43
Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
3.5K
EZH2 loss promotes gastric squamous cell carcinoma
Mengsha Zhang1, Ailing Zhong1, Hongyu Liu1
1State Key Laboratory of Biotherapy and Cancer Center and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Nature Communications
|July 2, 2025
Summary
Gastric Squamous Cell Carcinoma (GSCC) involves mutations in epigenetic genes like EZH2. EZH2 loss drives squamous features and tumorigenesis, offering potential therapeutic targets for this rare cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric Squamous Cell Carcinoma (GSCC) is a rare, aggressive gastric cancer subtype.
- The etiology and molecular drivers of GSCC are not well understood.
Purpose of the Study:
- To investigate the genomic and molecular underpinnings of GSCC.
- To identify key genes and pathways involved in GSCC development and progression.
Main Methods:
- Genomic analysis of twenty GSCC patient samples.
- In vitro organoid and in vivo mouse models to study gene function.
- Investigation of epigenetic mechanisms, including H3K27 methylation.
Main Results:
- Epigenetic regulation genes, including Enhancer of zeste homolog 2 (EZH2), are frequently mutated in GSCC.
- Ezh2 loss promotes squamous differentiation in gastric cells and drives GSCC development, particularly with Trp53 and Pten loss.
- EZH2 represses Transcription factor AP-2 gamma (Tfap2c) via H3K27 methylation; Tfap2c disruption affects squamous traits and chemoresistance.
Conclusions:
- EZH2 plays a critical role in suppressing squamous differentiation in the stomach.
- The EZH2-Tfap2c axis is a key molecular mechanism in GSCC pathogenesis.
- Targeting EZH2 or Tfap2c may offer new therapeutic strategies for GSCC.
Related Concept Videos
01:21Barrett Esophagus-I: Introduction
220
Barrett's esophagus is a medical condition where the esophageal mucosa is significantly damaged by stomach acid or other digestive fluids, often due to long-term exposure associated with gastroesophageal reflux disease (GERD). In GERD, a weakened or abnormally relaxed lower esophageal sphincter allows stomach acid to flow persistently into the esophagus.
This constant acid exposure transforms the esophagus's pink mucosal lining (stratified squamous epithelium) into a type of lining more...
This constant acid exposure transforms the esophagus's pink mucosal lining (stratified squamous epithelium) into a type of lining more...
220
01:21Barrett Esophagus-II: Clinical Manifestations and Management
318
Individuals with Barrett's esophagus are often asymptomatic, but they may experience symptoms commonly associated with GERD, such as heartburn and acid regurgitation. Additional symptoms can include difficulty swallowing, chest pain, unintentional weight loss, blood in the stool (which may appear black, tarry, or bloody), and episodes of vomiting.
To diagnose Barrett's esophagus, healthcare providers often recommend an endoscopy for those showing symptoms of acid reflux. The procedure...
To diagnose Barrett's esophagus, healthcare providers often recommend an endoscopy for those showing symptoms of acid reflux. The procedure...
318
01:30Peptic Ulcer Disease I: Introduction
301
Peptic Ulcer Disease (PUD) is characterized by mucosal excavation in the esophagus, stomach, pylorus, or duodenum. It can manifest as acute or chronic based on the extent and duration of mucosal involvement.
An acute ulcer, marked by superficial erosion and minimal inflammation, swiftly resolves upon identifying and addressing the underlying cause. In contrast, a chronic ulcer persists, potentially eroding through the muscular wall and forming fibrous tissue.
Peptic ulcers can also be...
An acute ulcer, marked by superficial erosion and minimal inflammation, swiftly resolves upon identifying and addressing the underlying cause. In contrast, a chronic ulcer persists, potentially eroding through the muscular wall and forming fibrous tissue.
Peptic ulcers can also be...
301
01:17Gastritis-II: Pathophysiology
592
Gastritis is marked by disruption of the mucosal barrier that usually protects the stomach tissue from digestive juices and manifests in acute and chronic forms.
In acute gastritis, the gastric mucosa becomes swollen and red and undergoes superficial erosion. Superficial ulceration may lead to bleeding.
In chronic gastritis, persistent or repeated insults lead to chronic inflammatory changes and, eventually, thinning or atrophy of the gastric tissue.
Gastritis can stem from various causes, each...
In acute gastritis, the gastric mucosa becomes swollen and red and undergoes superficial erosion. Superficial ulceration may lead to bleeding.
In chronic gastritis, persistent or repeated insults lead to chronic inflammatory changes and, eventually, thinning or atrophy of the gastric tissue.
Gastritis can stem from various causes, each...
592
01:26Peptic Ulcer Disease IV: Management
149
Medical treatment strategies for peptic ulcers encompass various methods. The primary goal of treatment is to diminish gastric acidity and strengthen mucosal defense mechanisms.
The therapeutic approach involves ensuring adequate rest, implementing drug therapy, promoting smoking cessation, making dietary modifications, and emphasizing long-term follow-up care.
Pharmacological management
The prevailing therapy for peptic ulcers involves a combination of managing the patient's current...
The therapeutic approach involves ensuring adequate rest, implementing drug therapy, promoting smoking cessation, making dietary modifications, and emphasizing long-term follow-up care.
Pharmacological management
The prevailing therapy for peptic ulcers involves a combination of managing the patient's current...
149
01:12Loss of Tumor Suppressor Gene Functions
5.1K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.1K