Characterization of the role played by forkhead box protein O3A in colon cancer stem cell

• Main Authors: Kuo-Chang Tseng, 曾國彰
• Other Authors: Yen-Rong Chern
• Format: Others
• Language: en_US
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/14523421877189797597

碩士 === 國立臺灣大學 === 生化科技學系 === 103 === Cancer stem cell (CSC) is one of the main reasons leading to the recurrence and the metastasis of several cancers. While having abilities as self-renew, quiescence and stress resistance as a normal stem cell, CSC is believed to share many key factors with a normal stem cell. However, due to the less of comprehensive researches and the difficulty in isolation and investigation of CSC, the factors which are essential to the CSC are not yet clear. In this thesis, I tested whether the transcription factor forkhead box protein O3A (FOXO3A), which is known as a necessary factor for normal stem cells, plays an important role in colon CSCs. Through analysis of quiescence population, the knock-down of FOXO3A in colon cancer cell lines decrease the quiescent population of cancer cells. Through sphere forming assay, I also show that the decrease of FOXO3A in cancer cells eliminates the self-renew ability since sphere numbers become significant lower than control. I confirmed that FOXO3A is critical for the maintenance of colon CSCs by promoting self-renew and quiescence. I also show that FOXO3A is constantly activated in colon cancer and independent to AKT/PI3K and TGF/SMAD pathways. Therefore FOXO3A may function in a dose-independent manner. Furthermore, these results indicate that FOXO3A may activate different or even novel gene sets during self-renew in colon CSCs.