文章：

FXYD5通过调控上皮-间质转化（EMT）影响胃癌细胞的转移和耐药

FXYD5 regulates gastric cancer cell metastasis and drug resistance by EMT modulation 

原文发布日期：2025-02-21 

英文摘要：

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. 

摘要翻译：

胃癌（GC）是全球癌症相关死亡的第三大原因，也是第四大常见恶性肿瘤。胃癌的高发病率和死亡率归因于多种因素，包括耐药性、局部复发和远处转移。当前亟需寻找新的胃癌治疗靶点。患者来源异种移植（PDX）模型在维持原发肿瘤分子异质性和肿瘤微环境方面具有独特优势，为个性化治疗靶点的筛选提供了重要平台。本研究通过原位移植技术建立了具有转移潜能的胃癌PDX模型，并采用PCR阵列技术分析原发灶与转移灶的基因表达差异。研究发现，与原发肿瘤相比，转移灶中含FXYD结构域的离子转运调节因子5（FXYD5）表达水平显著升高。降低FXYD5表达可抑制胃癌细胞的侵袭、转移和增殖能力。沉默FXYD5还能通过调节上皮-间质转化（EMT）过程和多药耐药蛋白2的表达，逆转胃癌细胞对阿霉素和长春新碱的耐药性。本研究表明FXYD5参与胃癌进展并调控化疗耐药性，提示其可能成为胃癌临床治疗的新靶点。

原文链接：

FXYD5 regulates gastric cancer cell metastasis and drug resistance by EMT modulation