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

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC

ACS Applied Electronic Materials Pub Date : 2024-08-19 eCollection Date: 2024-01-01 DOI:10.7150/jca.97895

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

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Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: ATP11A promoted migration, invasion, proliferation and EMT via Hippo signaling devitalization in gastric cancer cells.

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ATP11A 通过 Hippo 通路促进胃癌细胞的上皮-间质转化

背景：ATP11A 是一种 P 型 ATP 酶，在几种癌症中发挥着质膜翻转酶的功能，以维持细胞的功能和活力。然而，ATP11A在胃癌中的作用仍然未知。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。研究方法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（GO）、京都基因与基因组百科全书（KEGG）和基因组富集分析（GSEA）探讨了ATP11A的生物功能。通过免疫组织化学（IHC）、qRT-PCR 和 Western 印迹分析验证了 ATP11A 的表达。通过Transwell、伤口愈合、CCK8和集落形成检测胃癌细胞的迁移、侵袭和增殖。通过 Western 印迹检测上皮-间质转化（EMT）和 Hippo 通路标记物。结果显示ATP11A在胃癌组织中的表达高于正常组织，高水平的ATP11A与胃癌患者的预后有关。此外，我们还证实 ATP11A 能促进胃癌细胞的迁移、侵袭和增殖。此外，我们还发现 ATP11A 可通过破坏 Hippo 通路来促进 EMT。结论ATP11A 通过抑制 Hippo 信号转导促进了胃癌细胞的迁移、侵袭、增殖和 EMT。

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来源期刊

ACS Applied Electronic Materials Multiple-

CiteScore

7.20

自引率

4.30%

发文量

567