Mobile website
Basic Research
ZFX promotes esophageal squamous cell carcinoma progression by regulating Nectin-4 expression through the PI3K/AKT pathway
- Article
- Figures
- Metrics
- Preview PDF
- Reference
- Related
- Cited by
- Materials
Abstract:
[Abstract] Objective: To investigate the molecular mechanism by which X-linked zinc finger protein (ZFX) influenced the progression of esophageal squamous cell carcinoma (ESCC) through Nectin-4 expression and its role in activating the PI3K/AKT signaling pathway. Methods: Thirty pairs of ESCC tissue and adjacent tissue specimens surgically resected at Nanchong Central Hospital between August 2022 and July 2023 were collected. Human esophageal epithelial cells (HET-1A) and ESCC cell lines (KYSE-30, KYSE-150, KYSE-410, KYSE-510, and TE-1) were used. Nectin-4 was selected based on transcriptome sequencing data from 6 paired ESCC specimens collected between 2018 and 2019. Expression levels of Nectin-4 in ESCC tissues and cells were detected using the TIMER 2.0 database, RT-qPCR, Western blotting (WB), and immunohistochemistry (IHC). Nectin-4 was knocked down in KYSE-410 and KYSE-510 cells using shRNA technology. The effects of Nectin-4 knockdown on cell proliferation, migration, and invasion abilities were detected via CCK-8 assay, colony formation assay, scratch healing assay, and Transwell assay. WB analysis was performed to examine changes in PI3K/AKT pathway-related proteins and EMT-related proteins following Nectin-4 knockdown. Bioinformatics prediction combined with dual luciferase reporter assay identified and validated ZFX as an upstream transcriptional regulator of Nectin-4. Results: Comprehensive analysis revealed significantly higher Nectin-4 expression in ESCC tissues and cell lines compared with that in adjacent non-cancerous tissues and HET-1A cells (all P < 0.01). Functional studies revealed that Nectin-4 knockdown significantly inhibited proliferation activity, colony formation capacity, migration, and invasion capabilities in KYSE-410 and KYSE-510 cells (all P < 0.01). Mechanistically, knocking down Nectin-4 upregulated E-cadherin expression, downregulated N-cadherin expression in cells (both P < 0.01), and inhibited the phosphorylation of PI3K/AKT pathway-related proteins (P < 0.01). Conclusion: ZFX promotes ESCC progression by upregulating Nectin-4 and activating the PI3K/AKT pathway, identifying potential therapeutic targets for ESCC treatment.
Keywords:
Project Supported:
Clc Number:
