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

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作  者:程红春 吴虎成 李一建 管慧君 Chen Hongchun;Wu Hucheng;Li Yijian;Guan Huijun(Department of Thoracic Surgery,The People's Hospital of Tinghu District,Yancheng,Yancheng 224001,China;Department of Surgery,The People's Hospital of Tinghu District,Yancheng,Yancheng 224001,China)

机构地区:[1]盐城市亭湖区人民医院胸外科,盐城224001 [2]盐城市亭湖区人民医院外科,盐城224001

出  处:《解剖学杂志》2025年第1期48-52,75,共6页Chinese Journal of Anatomy

基  金:江苏省卫生健康委医学科研项目(M2021089)。

摘  要:目的:探究叉头框蛋白A1(FoxA1)能否通过联合Src同源性2结构域蛋白酪氨酸磷酸酶(SHP2)通路激活的环磷腺苷效应元件结合蛋白(CREB),促进食管癌内Yes相关蛋白(YAP)高表达,从而促进癌症进展。方法:收集盐城市亭湖区人民医院2021年5月-9月间临床资料保存完整的食管癌组织和相应癌旁正常组织,H-E染色观察病理学改变;免疫荧光显色测定FoxA1和YAP的表达。体外培养KYSE150细胞,分为FoxA1-NC组(干扰FoxA1对照组)、FoxA1-siRNA组(干扰FoxA1组)、DMSO溶剂组(培养基中添加DMSO)和PHPS1抑制剂组(培养基中添加SHP2抑制剂PHPS1),免疫印迹检测FoxA1、p-SHP2、p-CREB和YAP蛋白表达;细胞划痕实验、Transwell实验和克隆形成实验分别检测细胞迁移、侵袭和增殖能力。结果:与癌旁正常组织相比,食管癌组织出现黏膜充血、色泽灰暗,上皮层组织结构紊乱,细胞数量增多等病理学改变;食管癌组织中FoxA1、YAP蛋白表达水平明显升高。体外实验中,FoxA1-siRNA和PHPS1抑制剂均显著降低KYSE150细胞的p-SHP2、p-CREB和YAP蛋白水平以及细胞增殖、迁移、侵袭能力,但仅FoxA1-siRNA能显著降低FoxA1蛋白水平。结论:FoxA1通过联合SHP2通路激活的CREB促进食管癌内YAP高表达,从而促进食管癌进展。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.Con

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 

分 类 号:R329.2[医药卫生—人体解剖和组织胚胎学]

 

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