ENAH 通过 YY1 的转录激活促进喉癌细胞的生长和侵袭，通过 PI3K/AKT 信号通路。

ENAH transcriptionally activated by YY1 promotes growth and invasion of laryngocarcinoma cells through PI3K/AKT signaling.

机构信息

Department of Otolaryngology, Head & Neck Surgery, The Second Hospital of Hebei Medical University, China.

出版信息

Eur J Pharmacol. 2024 Nov 15;983:176991. doi: 10.1016/j.ejphar.2024.176991. Epub 2024 Sep 10.

DOI:10.1016/j.ejphar.2024.176991

PMID:39265883

Abstract

BACKGROUND

Laryngocarcinoma is a common malignancy in the upper respiratory tract. Enabled homolog (ENAH) is an actin-binding protein that is associated with the development of various cancers. However, its role and mechanism in laryngocarcinoma remain unknown.

METHODS

The ENAH level in laryngocarcinoma was examined in silico, in vitro and in vivo. The prognostic analysis of the ENAH level was assessed on laryngocarcinoma patients. Gain- and loss-of-function assays were conducted in AMC-HN-8 and TU686 cells. Sh-ENAH-containing AMC-HN-8 cells were implanted into naked mice. The role and mechanism of ENAH in laryngocarcinoma were investigated by CCK-8, transwell, immunofluorescence, dual luciferase, RT-qPCR, immunohistochemistry, and western blotting experiments.

RESULTS

The ENAH level was upregulated in laryngocarcinoma, which predicted a poor prognosis in laryngocarcinoma patients. Gain- and loss-of-function results showed that ENAH promoted proliferation, invasion and EMT of laryngocarcinoma cells. Moreover, ENAH was transcriptionally activated by YY1, and YY1/ENAH axis enhanced these malignant progresses of laryngocarcinoma cells. Besides, ENAH activated the PI3K/AKT pathway, and 740Y-P abolished the accelerative role of ENAH in proliferation, invasion and EMT of laryngocarcinoma cells. Furthermore, knockdown of ENAH reduced tumor size and weight, and the expression level of vimentin and PI3K/AKT pathway in tumor-bearing mice.

CONCLUSION

ENAH transcriptionally activated by YY1 promotes cell growth, invasion and EMT of laryngocarcinoma through the activation of PI3K/AKT signaling.

摘要

背景

喉癌是上呼吸道的常见恶性肿瘤。 Enabled 同源物（ENAH）是一种与多种癌症发展相关的肌动蛋白结合蛋白。然而，其在喉癌中的作用和机制尚不清楚。

方法

在体外和体内检测了喉癌中 ENAH 的水平。对喉癌患者的 ENAH 水平进行了预后分析。在 AMC-HN-8 和 TU686 细胞中进行了 gain- 和 loss-of-function 检测。将含有 Sh-ENAH 的 AMC-HN-8 细胞植入裸鼠。通过 CCK-8、transwell、免疫荧光、双荧光素酶、RT-qPCR、免疫组化和 Western blot 实验研究了 ENAH 在喉癌中的作用和机制。

结果

ENAH 在喉癌中上调，预示着喉癌患者的预后不良。gain- 和 loss-of-function 结果表明，ENAH 促进了喉癌细胞的增殖、侵袭和 EMT。此外，ENAH 被 YY1 转录激活，YY1/ENAH 轴增强了喉癌细胞的这些恶性进展。此外，ENAH 激活了 PI3K/AKT 通路，740Y-P 消除了 ENAH 对喉癌细胞增殖、侵袭和 EMT 的加速作用。此外，敲低 ENAH 减少了荷瘤小鼠的肿瘤大小和重量，以及波形蛋白和 PI3K/AKT 通路的表达水平。