解剖学杂志2025，Vol.48Issue(1)：48-52,75,6.DOI:10.3969/j.issn.1001-1633.2025.01.009
叉头框蛋白A1对食管癌进展的影响及其分子机制
Effect of forkhead box A1 on the progression of esophageal cancer and its molecular mechanisms
摘要
Abstract
Objective:To investigate whether forkhead box A1(FoxA1)could promote high expression of Yes-associated protein(YAP)in esophageal cancer and subsequently promote cancer progression by activating cAMP response element-binding protein(CREB)via the Src homology 2 domain-containing tyrosine phosphatase(SHP2)pathway.Methods:A total of 10 cases of esophageal cancer tissues and corresponding adjacent normal tissues with complete clinical data from May 2021 to September 2021 were collected from Yancheng Tinghu People's Hospital were collected.H-E staining was used to determine the pathological changes of esophageal carcinoma and adjacent normal tissues.Immunofluorescence staining was employed to evaluate the expressions of FoxA1 and YAP in esophageal carcinoma and adjacent normal tissues.KYSE150 cells were cultured in vitro and divided into four groups:FoxA1-NC group(control group for FoxA1 interference),FoxA1-siRNA group(FoxA1 interference group),DMSO solvent group(DMSO added to the culture medium),and PHPS1 inhibitor group(SHP2 inhibitor PHPS1 added to the culture medium).Western blotting was to measure the expression levels of FoxA1,p-SHP2,p-CREB and YAP protein in KYSE150 cells.Cell scratch assay,Transwell assay,and monoclonal proliferation assay were used to detect the proliferation,migration and invasion ability of KYSE150 cells,respectively.Results:Compared with the adjacent normal tissues,esophageal cancer tissues exhibited pathological changes such as mucosal hyperemia,dark color,disrupted epithelial tissue structure,and increased cell number.In addition,the levels of FoxA1,p-SHP2,p-CREB and YAP proteins in the esophageal cancer tissues were significantly increased.The results of in vitro experiments showed that,in in vitro experiments,both FoxA1-siRNA and the PHPS1 inhibitor significantly reduced the levels of p-SHP2,p-CREB,and YAP proteins in KYSE150 cells,as well as the cells'abilities to proliferate,migrate,and invade.However,only FoxA1-siRNA was able to significantly decrease the FoxA1 protein level.Conclusion:FoxA1 promotes the progression of esophageal cancer by activating CREB via the SHP2 pathway,leading to high expression of YAP.关键词
叉头框蛋白A1/Src同源性2结构域蛋白酪氨酸磷酸酶/环磷腺苷效应元件结合蛋白/Yes相关蛋白/食管癌Key words
forkhead box A1/Src homology-2-containing protein tyrosine phosphatase 2/cAMP-response element binding protein/yes-associated protein/esophageal cancer分类
基础医学引用本文复制引用
程红春,吴虎成,李一建,管慧君..叉头框蛋白A1对食管癌进展的影响及其分子机制[J].解剖学杂志,2025,48(1):48-52,75,6.基金项目
江苏省卫生健康委医学科研项目(M2021089) （M2021089）
