Related Experiment Video
Updated: Jul 17, 2025
In vitro Mesothelial Clearance Assay that Models the Early Steps of Ovarian Cancer Metastasis
Published on: February 17, 2012
FOXA2 suppresses gallbladder carcinoma cell migration, invasion, and epithelial-mesenchymal transition by targeting
Lingju Hong1,2,3,4, Mingyuan Chen1,2,3,4, Maotuan Huang1,2,3,4
1Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.
Background:
Gallbladder cancer (GBC), a highly malignant gastrointestinal tumor, lacks effective therapies. Foxhead box A2 (FOXA2) is a tumor suppressor that is poorly expressed in various human malignancies. This study aimed to ascertain FOXA2 expression in GBC and its relevance to tumor metastasis, and to elucidate its regulatory mechanism with epithelial-mesenchymal transition (EMT) as an entry point, in the hope of providing a potential therapeutic target for GBC.
Methods:
FOXA2 expression in GBC tissues was first detected using immunohistochemistry (IHC), followed by correlation analysis with clinicopathological characteristics and survival prognosis. Subsequently, the effects of FOXA2 on GBC cell migration and invasion, as well as EMT induction, were evaluated by scratch, Transwell, RT-PCR, and Western blot assays, together with animal experimentation. Ultimately, mRNA sequencing was carried out to identify the key downstream target genes of FOXA2 in controlling the EMT process in GBC cells, and dual-luciferase reporter and chromatin immunoprecipitation assays were used to determine its regulatory mechanism.
Results:
FOXA2 was underexpressed in GBC tissues and inversely correlated with tumor node metastasis stage, lymph node metastasis, and poor patient prognosis. FOXA2 exerts suppressive effects on EMT and metastasis of GBC in vivo and in vitro. FOXA2 can impede GBC cell migratory and invasive functions and EMT by positively mediating serine protein kinase inhibitor B5 (SERPINB5) expression.
Conclusion:
FOXA2 directly binds to the SERPINB5 promoter region to stimulate its transcription, thereby modulating the migration and invasion behaviors of GBC cells as well as the EMT process, which might be an effective therapeutic target against GBC.
Insights
Foxhead box A2 (FOXA2) is underexpressed in gallbladder cancer (GBC), suppressing metastasis. Upregulating FOXA2 may inhibit GBC cell invasion and EMT, offering a potential therapeutic strategy for this malignancy.
Area of Science:
- Oncology
- Gastroenterology
- Molecular Biology
Background:
- Gallbladder cancer (GBC) is a highly malignant gastrointestinal tumor with limited effective therapies.
- Foxhead box A2 (FOXA2), a known tumor suppressor, exhibits reduced expression in various human cancers, including GBC.
- Understanding FOXA2's role in GBC metastasis and its regulatory mechanisms is crucial for developing new treatments.
Purpose of the Study:
- To investigate FOXA2 expression levels in GBC tissues.
- To determine the correlation between FOXA2 expression and GBC clinicopathological features, metastasis, and patient prognosis.
- To elucidate the molecular mechanisms by which FOXA2 regulates epithelial-mesenchymal transition (EMT) and metastasis in GBC.
Main Methods:
- Immunohistochemistry (IHC) to detect FOXA2 expression in GBC tissues.
- In vitro and in vivo assays (scratch, Transwell, RT-PCR, Western blot, animal experiments) to assess FOXA2's impact on GBC cell migration, invasion, and EMT.
- mRNA sequencing, dual-luciferase reporter assays, and chromatin immunoprecipitation to identify and validate FOXA2's downstream targets and regulatory mechanisms.
Main Results:
- FOXA2 expression was significantly lower in GBC tissues and inversely correlated with advanced tumor stage, lymph node metastasis, and poor prognosis.
- FOXA2 suppressed GBC cell migration, invasion, and EMT in both in vitro and in vivo models.
- FOXA2 was found to enhance the expression of serine protein kinase inhibitor B5 (SERPINB5), thereby inhibiting GBC metastasis and EMT.
Conclusions:
- FOXA2 directly binds to the SERPINB5 promoter, upregulating its transcription.
- This FOXA2-SERPINB5 interaction effectively modulates GBC cell migration, invasion, and EMT.
- Targeting the FOXA2-SERPINB5 pathway presents a promising therapeutic strategy for combating gallbladder cancer.
More Related Videos
08:50In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines
Published on: April 18, 2025
06:35A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
Published on: December 22, 2020
Related Concept Videos
01:35Cancer Cell Migration through Invadopodia
01:17Gallbladder
The gallbladder's anatomy consists of three regions: the fundus, body, and neck. Extending from the neck, the cystic duct joins...
01:16TGF - β Signaling Pathway
01:19Cell Migration
01:17Gastritis-II: Pathophysiology
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...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...