Role of Haspin in human colorectal cancer using three-dimensional tissue culture model

• Main Author: 李采珈
• Other Authors: 趙瑞益
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/6h2g8q

碩士 === 國立交通大學 === 生物科技學系 === 105 === Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality in the world. Haspin is a histone H3 kinase that can phosphorylate H3 on threonine 3 (p-H3T3), which recruits chromosomal passenger complex (CPC) and promotes cell division. However, the functions of Haspin in CRC is still unclear. In this study, we used the 3D tissue culture model to investigate the role of Haspin in the patient CRC tissues. The CRC tissues were cultured with Matrigel to observe the cancer stemness properties whether correlated to Haspin protein expression. Interestingly, we found these tissue cells that expressed the lower protein levels of Haspin but highly expressed CD133 proteins by using the 3D tissue culture system. The p-H3T3 protein levels also expressed at the low level. We also verified the similar results by immunofluorescence staining and confocal microscopy. Moreover, overexpression of Haspin proteins by transfection with a Hapsin-expressed vector reduced the protein levels of CD133. In addition, we compared the Haspin and p-H3T3 protein levels in colorectal normal tissues and tumors from CRC patients. Most CRC tumor tissue samples highly expressed Haspin proteins by comparing normal tissues using immunohistochemistry staining. These results suggest that lower expression of Haspin may maintain the cancer stemness property under 3D tissue culture condition; however, higher Haspin proteins promote tumor growth in patient CRC tumors. We propose that Haspin can display the bi-functional effects in regulating the cancer stemness and tumorigenesis of CRC. Our findings demonstrate that Haspin is a potential target and novel strategy for CRC therapy.