Role of Carbonic Anhydrase III in oral cancer metastasis and its related mechanism

Autor: Yin-Hung Chu, 朱殷弘
Rok vydání: 2014
Druh dokumentu: 學位論文 ; thesis
Popis: 102
Carbonic anhydrase III (CA III) is a cytoplasmic enzyme that exhibits carbon dioxide hydratase activity and promotes transformation and invasion in cancer metastasis. During the epithelial–mesenchymal transition (EMT), epithelial cells become mesenchymal cells and metastasis is initiated for cancer progression. However, the functions and mechanisms of CA III in oral cancer are mostly unknown. We collected 248 oral cancer patients from the central area of Taiwan and analyzed the relationship between the CA III expression level and the clinical stage, recurrence, and survival rate. Using a CA III overexpression system, the effects on cell proliferation were determined by the MTT assay and on cell migration and invasion by the Boyden chamber assay. To clarify the signaling pathways, we investigated the expression of CA III, EMT-related proteins, and signaling proteins using western blotting and real-time polymerase chain reaction. Based on our results, we suggested that the patients with lower CA III expression had higher recurrence and lower survival rate. The mobility and invasive ability of the CA III-overexpressing oral cancer cells, SAS and SCC-9, were higher than those of the control cell lines. Western blotting identified EMT-related proteins such as E-cadherin, fibronectin, SNAI1, SNAI2 and TWIST as candidate downstream targets of CA III. Moreover, CA III-mediated cell migration and EMT-related protein expression were modulated through the phosphorylation of the signaling molecules FAK and Src. In conclusion, we revealed that CA III may induce cell migration and invasion through EMT induction in the SAS and SCC-9 cells. The activation of FAK and Src signaling may be involved in the CA III-mediated EMT in these oral cancer cells.
Databáze: Networked Digital Library of Theses & Dissertations
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