Klotho inhibits the capacity of cell migration and invasion in cervical cancer

BOOGI CHANG, JINSUN KIM, DONGJUN JEONG, YUJUN JEONG, SEOB JEON, SAM-IL JUNG, YOUNG YANG, KEUN IL KIM, JONG-SEOK LIM, CHANGJIN KIM, MYEONG-SOK LEE
2012 Oncology Reports  
Aberrant activation of the Wnt/β-catenin signaling pathway is common in human cervical cancers. However, the mechanisms of Wnt activation in cervical cancer remain largely unknown. In the present study, we demonstrate that Klotho, a Wnt antagonist, is downregulated in invasive human cervical tumors and in a cell line we analyzed. Our data demonstrated that in vivo Klotho expression was not observed in invasive cervical carcinoma. In vitro restoration of Klotho expression in SiHa cells resulted
more » ... iHa cells resulted in a decreased cell motility and invasiveness through upregulation of E-cadherin, downregulation of N-cadherin and reduced expression of MMP7 and -9. Ectopic expression of Klotho also reduced the expression of the epithelial-to-mesenchymal transition (EMT) transcription factors Slug and Twist. Furthermore, Klotho causes a significant inhibition of the Wnt/β-catenin pathway in cervical cancer cells, as supported by the expression of Wnt/β-catenin transcriptional target genes such as c-Myc and cyclin D1. Consequently, our findings demonstrate for the first time that Klotho regulates tumor invasion through the EMT process and provide novel mechanistic insights into the role of Klotho in cervical cancer progression and contribute to treatment for metastatic cervical cancer patients. Abbreviations: HPV, human papilloma virus; Fz/LRP, Frizzled/ low-density lipoprotein receptor-related protein; TCF/LEF, T-cell factor/lymphoid enhance factor; IGF-1, insulin-like growth factor-1; FGF23, fibroblast growth factor 23; EMT, epithelial-tomesenchymal transition; MMPs, matrix metalloproteinases; ABC, active form of β-catenin
doi:10.3892/or.2012.1865 pmid:22710352 fatcat:4io5jav72vbqjhchvhexu346wi