| Summary: | 碩士 === 國立陽明大學 === 生命科學暨基因體科學研究所 === 99 === Survivin, an inhibitor of apoptosis protein, has dual functions in regulating cell cycle progression and in inhibiting apoptosis. The expression of Survivin is undetectable in most adult normal tissues, however, Survivin is highly-expressed in many human cancers. In recent years, Survivin has been reported to promote cell migration and metastasis in many tumor cells. In our laboratory, we also found that overexpression of Survivin enhances cell migration and invasion in esophageal carcinoma cell lines. Aurora-A is a mitotic serine/threonine kinase, which plays important roles in mitotic division and anti-apoptosis, it also regulates cell migration in mammary and nasopharyngeal carcinoma. In this study, we found that overexpression of Aurora-A increases cell migration and invasion in esophageal carcinoma cell lines. We also found that the kinase dead Aurora-A does not enhance cellular motility, indicating the kinase activity is essential for Aurora-A to regulate cell migration. Furthermore, knockdown Survivin in esophageal carcinoma cells partially abolished Aurora-A enhanced cell migration. Our previous finding showed that Aurora-A phosphorylates Survivin to increase Survivin stability and regulate its cytoprotective activity. We hypothesized that Aurora-A may regulates cell migration by phosphorylating Survivin. Hence, three different Survivin mutants, Survivin-T21A, the double phosphorylation defect mutant; Survivin-T21E, the constitutively phosphorylated mutant; and Survivin-S81A, the single phosphorylation defect mutant, were used to investigate whether Aurora-A phosphorylates Survivin to regulate cell migration. The data showed that Survivin-T21E enhances cell migration is more than wild type Survivin does, while Survivin-T21A and Survivin-S81A mutants have less ability to enhance cell migration when compared with wild type Survivin. These results indicate that Aurora-A phosphorylates Survivin to regulate cell migration. However, the possible downstream mechanisms that involve in Survivin and Aurora-A regulated cell migration still need further investigation.
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