He Huan, Ding Fang, Li Sheng, Chen Hongyan, Liu Zhihua
The State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021, China.
Am J Cancer Res. 2014 May 26;4(3):270-8. eCollection 2014.
Cell adhesion proteins that connect each cell to neighboring cells and the extracellular matrix are an important determinant of cell morphology and metastasis. Migfilin is a member of LIM-containing protein family, mediated the linkage between cytoskeleton and focal adhesion through interacting with other proteins and involved in cell adhesion and motility. The present study used immunohistochemistry and Western blot analysis of migfilin in clinical specimens of esophageal squamous cell carcinoma (ESCC) to identify that the expression of migfilin was significantly upregulated in ESCC in concomitance with a nuclear-cytoplasm translocation compared to normal adjacent tissue. Alternately, using the published datasets we identified that the expression of β-catenin was upregulated in esophageal cancer cells with focal invasion, while inversely correlated with migfilin in esophageal cancer cell lines. We demonstrated that the reduced expression of β-catenin by migfilin was through the inhibition of Akt activation. In conclusion, these results illustrated that migfilin upregulated in ESCCs and repressed β-catenin in an Akt-GSK3β signaling dependent manner.
将每个细胞与相邻细胞及细胞外基质连接起来的细胞黏附蛋白是细胞形态和转移的重要决定因素。Migfilin是含LIM蛋白家族的成员,通过与其他蛋白质相互作用介导细胞骨架与黏着斑之间的联系,并参与细胞黏附与运动。本研究采用免疫组织化学和蛋白质印迹分析食管鳞状细胞癌(ESCC)临床标本中的Migfilin,以确定与正常相邻组织相比,ESCC中Migfilin的表达显著上调,并伴有核质易位。另外,利用已发表的数据集,我们发现β-连环蛋白在具有局灶性浸润的食管癌细胞中表达上调,而在食管癌细胞系中与Migfilin呈负相关。我们证明Migfilin通过抑制Akt激活来降低β-连环蛋白的表达。总之,这些结果表明Migfilin在ESCC中上调,并以Akt-GSK3β信号依赖的方式抑制β-连环蛋白。