The role of acetylated snail in modulating metabolism of head and neck cancer

• Main Authors: Shih-Pei Wu, 吳詩培
• Other Authors: Muh-Hwa Yang
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/u7e9u8

碩士 === 國立陽明大學 === 臨床醫學研究所 === 105 === Snail is primarily known as a transcriptional regulator that induces epithelial-mesenchymal transition (EMT) by suppressing adherent proteins and inducing tumor metastasis in field of cancer biology. Our previous article showed ac-Snail modulates cytokinome by interacting with CBP/P300 and recruits tumor-associated macrophage(TAM) that alter the microenvironment in head and neck squamous cell carcinoma (HNSCC). Interestingly, we found more energetic phenotype and different metabolite in ac-Snail cells compared to unac-Snail cells. In this study, we want to clarify how ac-Snail reprograms metabolism of cancer cells and changes the microenvironment. Bromodomain containing protein (BRD) is a protein family that recognizes and interacts to acetyl-Lysine of proteins. A bromodomain inhibitor, JQ1 has been reported to inhibit chromatin activation also impaired the acetylated-Snail induced metabolism in HNSCC. In many BRDs, BRG1 not only has bromodomain, but also has ATPase and helicase that responsible for chromatin unwinding in SWI / SNF complex. We demonstrated that BRG1 interacted with ac-Snail protein by co-immunoprecipitation in vitro and proximity ligation assay in vivo. Further, we identified NT5E and ABCA1 were significantly regulated by ac-Snail and BRG1 through a serious screening. Interestingly, either knockdown NT5E or ABCA1 in HNSCC both reversed the ac-Snail metabolic phenotype. In this study, we speculate that ac-Snail reprograms the metabolism in head and neck cancer cells by cooperating with BRG1 to regulate NT5E and ABCA1.