FERMT1 promotes epithelial-mesenchymal transition of hepatocellular carcinoma by activating EGFR/AKT/β-catenin and EGFR/ERK pathways

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2024-09-30 DOI:10.1016/j.tranon.2024.102144

Wubin Guo , Mengnan Liu , Wei Luo , Jing Peng , Fei Liu , Xin Ma , Li Wang , Sijin Yang

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引用次数: 0

Abstract

Objective

This study aimed to investigate the effects of fermitin family member 1 (FERMT1) on epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) via the EGFR/AKT/β-catenin and EGFR/ERK pathways.

Methods

The expression of FERMT1 encoding protein kindlin-1 in HCC tissues was determined by immunohistochemistry, and FERMT1 mRNA expression in HCC tissues and cell lines was analyzed by qRT-PCR. After the FERMT1 expression of SNU182 and SNU387 interfered with siRNA, the cell viability, invasion, migration, and EMT were tested by CCK-8, transwell invasion, scratching, immunofluorescence/WB, respectively. Similarly, the effects of FERMT1 on the viability and metastasis of HCC were investigated in transplanted tumor and lung metastasis mouse models. The protein expressions of EGFR/AKT/β-catenin and EGFR/ERK pathways were analyzed by WB. In addition, the relationship between FERMT1 and EGFR was further determined by immunofluorescence double staining and Co-IP.

Results

FERMT1 was significantly upregulated in HCC, and silencing FERMT1 inhibited the viability, invasion, migration, and EMT of HCC. Silencing FERMT1 also inhibited the activation of EGFR/AKT/β-catenin and EGFR/ERK pathways. In addition, inhibition of EGFR, AKT, or ERK confirmed that EGFR/AKT/β-catenin and EGFR/ERK pathways were involved in the promoting effects of FERMT1 on HCC. Co-IP and immunofluorescence experiments confirmed the targeting relationship between FERMT1 and EGFR.

Conclusion

FERMT1 was highly expressed in HCC and promoted viability, invasion, migration, and EMT of HCC by targeting EGFR to activate the EGFR/AKT/β-catenin and EGFR/ERK pathways. Our study revealed the role of FERMT1 in HCC and suggested that FERMT1 exerts biological effects through activating the EGFR/AKT/β-catenin and EGFR/ERK pathways.

查看原文本刊更多论文

FERMT1 通过激活表皮生长因子受体/AKT/β-catenin 和表皮生长因子受体/ERK 通路，促进肝细胞癌的上皮-间质转化

目的本研究旨在探讨费米素家族成员1（FERMT1）通过表皮生长因子受体/AKT/β-酪蛋白和表皮生长因子受体/ERK通路对肝细胞癌（HCC）上皮-间质转化（EMT）的影响。方法采用免疫组化法测定 FERMT1 编码蛋白 kindlin-1 在 HCC 组织中的表达，并采用 qRT-PCR 法分析 FERMT1 mRNA 在 HCC 组织和细胞系中的表达。用siRNA干扰SNU182和SNU387的FERMT1表达后，分别用CCK-8、transwell侵袭、划痕、免疫荧光/WB检测细胞活力、侵袭、迁移和EMT。同样，在移植瘤和肺转移小鼠模型中研究了 FERMT1 对 HCC 的活力和转移的影响。WB 分析了表皮生长因子受体/AKT/β-catenin 和表皮生长因子受体/ERK 通路的蛋白表达。结果FERMT1在HCC中显著上调，沉默FERMT1可抑制HCC的活力、侵袭、迁移和EMT。沉默 FERMT1 还能抑制 EGFR/AKT/β-catenin 和 EGFR/ERK 通路的激活。此外，抑制表皮生长因子受体、AKT或ERK证实了表皮生长因子受体/AKT/β-catenin和表皮生长因子受体/ERK通路参与了FERMT1对HCC的促进作用。结论FERMT1在HCC中高表达，通过靶向表皮生长因子激活表皮生长因子受体/AKT/β-catenin和表皮生长因子受体/ERK通路，促进HCC的活力、侵袭、迁移和EMT。我们的研究揭示了FERMT1在HCC中的作用，并认为FERMT1通过激活表皮生长因子受体/AKT/β-catenin和表皮生长因子受体/ERK通路发挥生物学效应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.