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Updated: May 26, 2025

Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
FXYD5 regulates gastric cancer cell metastasis and drug resistance by EMT modulation
Yuning Mao1,2, Yaohua Hu1, Han Meng1
1Division of Cancer Biology, Laboratory Animal Center, Air Force Medical University, 710032, Xi'an, Shaanxi, China.
Abstract:
Gastric cancer (GC) is the third leading cause of cancer-related mortality and the fourth most prevalent malignancy globally. The high prevalence and mortality rates of GC are attributed to various factors, including drug resistance, local recurrence, and distant metastases. There is an urgent need to identify novel therapeutic targets for GC. Patient-derived xenografts (PDX) model offers unique advantages in maintaining the molecular heterogeneity and tumor microenvironment of primary tumors, offering significant advantages for the screening of personalized therapeutic targets. In this study, we established GC PDX models with metastatic potential through orthotopic transplantation and investigated the different gene expressions between primary and metastatic tumors using PCR-array analysis. We found that the metastatic tumors displayed elevated levels of FXYD domain-containing ion transport regulator 5 (FXYD5) compared to the primary tumors. Additionally, reducing FXYD5 expression was found to inhibit the invasion, metastasis, and proliferation of GC cells. Silencing FXYD5 also reversed the resistance of GC cells to doxorubicin and vincristine by modulating the epithelial-mesenchymal transition (EMT) process and the expression of multidrug resistance protein 2. This study indicates that FXYD5 is involved in GC progression and regulates chemotherapy resistance, suggesting its potential as a novel therapeutic target for the clinical treatment of GC.
Insights
Gastric cancer (GC) progression and metastasis are linked to elevated FXYD5 levels. Reducing FXYD5 inhibits GC spread and reverses chemotherapy resistance, identifying it as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Gastric cancer (GC) is a leading cause of cancer mortality worldwide.
- Drug resistance, recurrence, and metastasis contribute to high GC mortality rates.
- Novel therapeutic targets are urgently needed for effective GC treatment.
Purpose of the Study:
- To identify novel therapeutic targets for gastric cancer (GC).
- To investigate the role of FXYD domain-containing ion transport regulator 5 (FXYD5) in GC progression and metastasis.
- To evaluate FXYD5 as a potential target for overcoming chemotherapy resistance in GC.
Main Methods:
- Establishment of patient-derived xenograft (PDX) models of metastatic gastric cancer via orthotopic transplantation.
- Differential gene expression analysis between primary and metastatic tumors using PCR-array.
- In vitro experiments involving FXYD5 knockdown to assess its impact on GC cell invasion, metastasis, proliferation, and drug resistance.
Main Results:
- Metastatic GC tumors exhibited significantly higher FXYD5 expression compared to primary tumors.
- Reducing FXYD5 expression suppressed GC cell invasion, metastasis, and proliferation.
- Silencing FXYD5 reversed resistance to doxorubicin and vincristine by modulating epithelial-mesenchymal transition (EMT) and multidrug resistance protein 2 (MRP2) expression.
Conclusions:
- FXYD5 plays a crucial role in gastric cancer progression, invasion, and metastasis.
- FXYD5 is implicated in regulating chemotherapy resistance in GC.
- FXYD5 represents a promising novel therapeutic target for clinical intervention in gastric cancer.
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