| Autor: |
Zhang C; School of Life Science & Medicine, Dalian University of Technology, Panjin, China., Huang H; School of Life Science & Medicine, Dalian University of Technology, Panjin, China., Zhang J; School of Life Science & Medicine, Dalian University of Technology, Panjin, China., Wu Q; School of Life Science & Medicine, Dalian University of Technology, Panjin, China., Chen X; School of Life Science & Medicine, Dalian University of Technology, Panjin, China., Huang T; School of Life Science & Medicine, Dalian University of Technology, Panjin, China., Li W; School of Life Science & Medicine, Dalian University of Technology, Panjin, China.; School of Life Science & Biotechnology, Dalian University of Technology, Dalian, China., Liu Y; School of Life Science & Medicine, Dalian University of Technology, Panjin, China. liuyubo@dlut.edu.cn., Zhang J; School of Life Science & Medicine, Dalian University of Technology, Panjin, China. jnzhang@dlut.edu.cn. |
| Abstrakt: |
Caveolin-1 (Cav-1) is an important structural protein of caveolae and plays an oncogene-like role by influencing protein glycosylation in hepatocellular carcinoma (HCC) cells. However, the mechanism by which Cav-1 promotes invasion and metastasis capacity has not been completely clarified. In this study, we demonstrate that Pofut1 is a fucosyltransferase induced by Cav-1. Mouse Hepa1-6 HCC cells lacking Cav-1 expression exhibited low transcription levels of Pofut1, whereas strong Pofut1 expression was found in high-metastasis-potential Hca-F cells with high levels of Cav-1. Cav-1 activated MAPK signaling and promoted phosphorylation of the transcription factors CREB, Sp1, HNF4A and c-Myc, which bound to the Pofut1 promoter region to induce its transcription. As Notch signaling receptors can be modified with O-fucose by Pofut1, we further showed that Cav-1-induced upregulation of Pofut1 expression activated the Notch pathway and thus enhanced invasion and metastasis by mouse HCC cells in vitro and in vivo. Collectively, our findings reveal a novel mechanism by which Cav-1 promotes tumor metastasis by upregulating expression of Pofut1, suggesting that Cav-1 may function as a new biomarker for HCC. |
