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

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.