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ATP11A通过Hippo信号通路促进胃癌细胞的上皮-间质转化

ATP11A Promotes Epithelial-mesenchymal Transition in Gastric Cancer Cells via the Hippo Pathway.

作者信息

Wang Zhihua, Xue Mingmiao, Liu Junqiang, Jiang Han, Li Feifan, Xu Min, Wang Huizhi

机构信息

Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, 438 Jiefang Road, Zhenjiang 212001, China.

Department of Endocrinology, Affiliated Hospital of Jiangsu University, Jiangsu University, 438 Jiefang Road, Zhenjiang 212001, China.

出版信息

J Cancer. 2024 Aug 19;15(16):5477-5491. doi: 10.7150/jca.97895. eCollection 2024.

DOI:10.7150/jca.97895
PMID:39247595
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11375558/
Abstract

ATP11A, a P-type ATPase, functions as flippases at the plasma membrane to maintain cellular function and vitality in several cancers. However, the role of ATP11A in gastric cancer remains unknown. This study aimed to identify ATP11A related to the biological behavior of gastric cancer, and elucidate the underlying mechanism. The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to analyze the expression and prognosis of ATP11A. The biofunctions of ATP11A were explored through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). The expression of ATP11A were validated by immunohistochemistry (IHC), qRT-PCR and Western blotting. Transwell, wound healing, CCK8 and colony-formation were to detected the migration, invasion and proliferation of gastric cancer cells. The epithelial-mesenchymal transition (EMT) and Hippo pathway markers were examined by Western blotting. The expression of ATP11A was higher in gastric cancer tissues than in normal tissues, and high ATP11A levels were related to worse prognosis of gastric cancer patients. Additionally, we proved that ATP11A promoted the migration, invasion and proliferation in gastric cancer cells. Furthermore, ATP11A was found to promote EMT by devitalizing the Hippo pathway. ATP11A promoted migration, invasion, proliferation and EMT via Hippo signaling devitalization in gastric cancer cells.

摘要

ATP11A是一种P型ATP酶，在质膜上作为翻转酶发挥作用，以维持多种癌症中的细胞功能和活力。然而，ATP11A在胃癌中的作用尚不清楚。本研究旨在鉴定与胃癌生物学行为相关的ATP11A，并阐明其潜在机制。利用癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）数据库分析ATP11A的表达和预后。通过基因本体论（GO）、京都基因与基因组百科全书（KEGG）和基因集富集分析（GSEA）探索ATP11A的生物功能。通过免疫组织化学（IHC）、qRT-PCR和蛋白质印迹法验证ATP11A的表达。采用Transwell、伤口愈合、CCK8和集落形成实验检测胃癌细胞的迁移、侵袭和增殖能力。通过蛋白质印迹法检测上皮-间质转化（EMT）和Hippo通路标志物。ATP11A在胃癌组织中的表达高于正常组织，且ATP11A水平高与胃癌患者预后较差相关。此外，我们证明ATP11A促进胃癌细胞的迁移、侵袭和增殖。此外，发现ATP11A通过使Hippo通路失活来促进EMT。ATP11A通过使胃癌细胞中的Hippo信号失活来促进迁移、侵袭、增殖和EMT。

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本文引用的文献

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Upregulation of LINC00501 by H3K27 acetylation facilitates gastric cancer metastasis through activating epithelial-mesenchymal transition and angiogenesis.H3K27 乙酰化上调 LINC00501 促进胃癌转移通过激活上皮-间充质转化和血管生成。
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