Tony Overexpression of Carbonic anhydrase-related protein-8 gene promotes epithelial-to-mesenchymal transition in human osteosarcoma cells. 1,2Seng-sheen Fan, 1,2Wei-Ting Chao, 2,3,4Min-Huan Wu 1Department of Life Science Research Center, Tunghai University, Taichung 40704, Taiwan 2Life Science Research Center, Tunghai University, Taichung 40704, Taiwan 3Physical Education Office, Tunghai University, Taichung 40704, Taiwan 4Sports Recreation and Health Management Continuing Studies, Tunghai University, Taichung 40704, Taiwan Abstract Osteosarcoma is the most common primary tumor of the bone. It leads to many deaths because of its rapid proliferation and metastasis. Carbonic anhydrases (CAs) are zinc metalloenzymes and also contribute to several important biological processes. CA8 is an isozyme of α-carbonic anhydrases (CAs). Here, we found that overexpression of CA8 in osteosarcoma (HOS cells) drives epithelial-to-mesenchymal transition (EMT) by inducing migration and increased levels of N-cadherin, Twist, and other mesenchymal markers. Pretreatment of osteosarcoma cells with AMP-activated protein kinase (AMPKα) inhibitors or Twist siRNA abolished CA8-promoted migration and increased the expression of N-cadherin. On the other hand, CA8 demonstrably activated AMPKα and Twist signaling pathways. Furthermore, the expression levels of N-cadherin and Twist were correlated in human osteosarcoma specimens. Taken together, our results indicate that CA8 enhances the EMT markers and migratory ability of human osteosarcoma cells by increasing N-cadherin expression via AMPKα and Twist pathways. Key words: Carbonic anhydrases (CAs), osteosarcoma, epithelial-mesenchymal transition, Twist, migration
Posted on: Tue, 22 Jul 2014 08:13:08 +0000
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