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ELK3 通过调控细胞外基质重塑相关基因控制胃癌细胞迁移和侵袭。

ELK3 Controls Gastric Cancer Cell Migration and Invasion by Regulating ECM Remodeling-Related Genes.

机构信息

Department of Biomedical Science, College of Life Science, CHA University, Pangyo-Ro 335, Bundang-gu, Seongnam-si 463-400, Korea.

出版信息

Int J Mol Sci. 2022 Mar 28;23(7):3709. doi: 10.3390/ijms23073709.

DOI:10.3390/ijms23073709
PMID:35409069
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8998440/
Abstract

Current therapeutic strategies for gastric cancer, including surgery and chemotherapy improve patient survival; however, the survival rate of patients with metastatic gastric cancer is very low. The molecular mechanisms underlying the dissemination of gastric cancer cells to distant organs are currently unknown. Here, we demonstrate that the E26 transformation-specific (ETS) transcription factor () gene is required for the migration and invasion of gastric cancer cells. The gene modulates the expression of extracellular matrix (ECM) remodeling-related genes, such as bone morphogenetic protein (), lysyl oxidase like 2 (), Snail family transcriptional repressor 1 (), serpin family F member 1 (), decorin (), and nidogen 1 () to facilitate cancer cell dissemination. Our in silico analyses indicated that expression was positively associated with these ECM remodeling-related genes in gastric cancer cells and patient samples. The high expressions of and other ECM remodeling-related genes were also closely associated with a worse prognosis of patients with gastric cancer. Collectively, these findings suggest that ELK3 acts as an important regulator of gastric cancer cell dissemination by regulating ECM remodeling.

摘要

目前的胃癌治疗策略，包括手术和化疗，都能提高患者的生存率；然而，转移性胃癌患者的生存率非常低。胃癌细胞扩散到远处器官的分子机制目前尚不清楚。在这里，我们证明 E26 转化特异性（ETS）转录因子（ELK3）基因是胃癌细胞迁移和侵袭所必需的。该基因调节细胞外基质（ECM）重塑相关基因的表达，如骨形态发生蛋白（BMP）、赖氨酰氧化酶样 2（LOXL2）、Snail 家族转录抑制因子 1（Snail1）、丝氨酸蛋白酶抑制因子家族 F 成员 1（SerpinF1）、核心蛋白聚糖（Decorin）和巢蛋白 1（Nidogen1），以促进癌细胞的扩散。我们的计算机分析表明，ELK3 在胃癌细胞和患者样本中的表达与这些 ECM 重塑相关基因呈正相关。ELK3 和其他 ECM 重塑相关基因的高表达也与胃癌患者的预后不良密切相关。综上所述，这些发现表明 ELK3 通过调节 ECM 重塑，作为胃癌细胞扩散的重要调节因子发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b84a/8998440/747f88f687a5/ijms-23-03709-g007a.jpg
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