Klotho inhibits the capacity of cell migration and invasion in cervical             cancer.
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 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.
Research Center for Women's Diseases and Department of Biological                     Sciences, Sookmyung Women's University, Seoul, Republic of Korea.
Boogi
B
Chang
Jinsun
J
Kim
Dongjun
D
Jeong
Yujun
Y
Jeong
Seob
S
Jeon
Sam-Il
SI
Jung
Young
Y
Yang
Keun Il
KI
Kim
Jong-Seok
JS
Lim
Changjin
C
Kim
Myeong-Sok
MS
Lee
D015820:Cadherins / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D052162:Human papillomavirus 16; D006801:Humans; D000090265:Klotho Proteins; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000378:metabolism; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D060449:Wnt Signaling Pathway
D015820:Cadherins; D009687:Nuclear Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D005966:Glucuronidase; D000090265:Klotho Proteins; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9