中国肿瘤生物治疗杂志2026，Vol.33Issue(4)：408-417,10.DOI:10.3872/j.issn.1007-385x.2026.04.007
ZFX通过PI3K/AKT通路调控Nectin-4表达促进食管鳞状细胞癌进展
ZFX promotes esophageal squamous cell carcinoma progression by regulating Nectin-4 expression through the PI3K/AKT pathway
摘要
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.关键词
食管鳞状细胞癌/Nectin-4/X连锁锌指蛋白/上皮-间质转化/PI3K/AKT信号通路Key words
esophageal squamous cell carcinoma(ESCC)/Nectin-4/X-linked zinc finger protein(ZFX)/epithelial-mesenchymal transition(EMT)/PI3K/AKT signaling pathway分类
医药卫生引用本文复制引用
龙元凤,别俊,宋桂芹,刘康,杨燕,卞宇航,邓钰滨,陈巧玲,杨航,张若兰,赵全能,杨蜜..ZFX通过PI3K/AKT通路调控Nectin-4表达促进食管鳞状细胞癌进展[J].中国肿瘤生物治疗杂志,2026,33(4):408-417,10.基金项目
国家自然科学基金(82203851) （82203851）
四川省科学技术厅项目(2024NSFSC1973,2023YFS0473) （2024NSFSC1973,2023YFS0473）
四川省医学会医学科研项目(S2024009) （S2024009）
南充市市校合作项目(22SXQT0336,23JCYJPT0027,22SXQT0340,22SXQT0087,22SXQT0096) （22SXQT0336,23JCYJPT0027,22SXQT0340,22SXQT0087,22SXQT0096）
川北医学院科研项目(CBY24-KP03,CBY22-QDA01,CBY23-ZDA11) （CBY24-KP03,CBY22-QDA01,CBY23-ZDA11）
四川省科技厅苗子工程(MZGC20240072,MZGC20240071) （MZGC20240072,MZGC20240071）
