| Summary: | 碩士 === 國立陽明大學 === 生命科學系暨基因體科學研究所 === 105 === Survivin, a member of inhibitor of apoptosis protein (IAP) family, has dual functions in cell cycle regulation and anti-apoptosis. Survivin is markedly expressed in the G2-M phase of cell cycle in normal cells but highly expressed in various human cancers. The presence of survivin in tumors is associated with chemoresistance and poor prognosis. Moreover, survivin has been reported to promote tumor cells migration and cancer metastasis in recently years. However, the role of survivin in esophageal cancer cell migration is still unclear. In this study, we used transwell migration assay to determinate the effect of survivin on cell migration. Knockdown survivin by shRNA in TE-9 cells, which has highly endogenous survivin expression, decreased cell migration significantly. Conversely, overexpression of survivin in CE48T/VGH and TE-2 cells promoted cell migration. Furthermore, we found that knockdown survivin in TE-9 cells decreased cell invasion by reduced MMP-2 expression. Previous study have shown the strong correlation between survivin and NF-κB signaling pathway, we also shown that knockdown surviving in TE-9 cells elevated IκB-α then inhibited NF-κB nuclear translocation. In addition, knockdown survivin in TE-9 cells decreased the protein level of Akt, which may activated NF-κB pathway. These suggest that knockdown survivin downregulates MMP-2 expression through Akt/ NF-κB pathway inhibition. In our lab, we haves found that survivin was phosphorylated at Thr21 and Ser81 by a mitotic serine/threonine kinase Aurora-A, which plays an important role in cell division, anti-apoptosis and cell migration. This phosphorylation increased survivin protein stability but also sustained the function of survivin to inhibit apoptosis. However, overexpression Aurora-A in TE-2 cells did not regulate cell invasion. We will further investigate the effect of Aurora-A on cell migration regulation. Additionally, whether Aurora-A mediated phosphorylation is required for the function of survivin to promote migration also will be studied.
|
|---|
