Expression and Implications of Protein Sgo1 in Oral Cancer

• Main Authors: You, Siang Yi, 尤湘懿
• Other Authors: Wang, Lily Hui Ching
• Format: Others
• Language: en_US
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/38490794639511368759

碩士 === 國立清華大學 === 分子與細胞生物研究所 === 104 === Oral cancer is one of the ten major causes of cancer death in Taiwan, ranking the fourth in men. Despite recent advances in prevention, diagnosis and treatment, the incidence and mortality of oral cancer still increased in past decades, and the overall survival rates for patients have not been improved. These highlight the urgent need for exploring novel therapeutic targets and more biomarkers for early detection and treatment. Protein Shugoshin-1 (Sgo1) functions to protect sister chromatid cohesion during mitosis and thereby ensures the fidelity of chromosome separation and the maintenance of genomic integrity. In the present study, we compared expression of Sgo1 in 7 different oral squamous cell carcinoma (OSCC) cell lines and dysplastic oral keratinocyte. The expression levels of Sgo1 were also upregulated in oral cancer tissues as revealed by tissue array, and certain OSCC cell lines. We found that the depletion of Sgo1 caused significant cell death in 5 oral cancer cell lines, but not in 3 other lines. We then categorized these cells as “resistant” and “susceptible” lines based on sensitivity to Sgo1 deficiency. Using time-lapse microscopy, we showed that susceptible cells were delayed and died in mitosis upon Sgo1 depletion. Notably, increased mitotic population and premature sister chromatid separation were detected in both resistant and susceptible lines following Sgo1 depletion. This indicates that Sgo1 is essential for mitotic progression in oral cancer cells. We demonstrated that the sensitivity to Sgo1 inhibition depends on robustness of the spindle assembly checkpoint (SAC) functionality, and the abolishment of SAC can restore mitotic catastrophe induced by Sgo1 depletion. Finally, with the help of regression analysis, we found that Sgo1, Bub1 and Plk-1 expression levels may serve as good indicator of SAC robustness and hence the sensitivity to Sgo1 depletion. Our results raise the possibility to apply Sgo1 sensitivity as a supporting therapeutic approach for treating oral cancer in the future.