The Signal Transduction Mechanisms for TPA-Induced Cell Adhesion and Migration of Human Hepatoma G2

• Main Authors: Michael Chang, 張育勳
• Other Authors: Wu Wen Sheng
• Format: Others
• Language: zh-TW
• Online Access: http://ndltd.ncl.edu.tw/handle/83854393587292915767

碩士 === 慈濟大學 === 醫學生物技術研究所 === 95 === We have discovered that TPA may simultaneously trigger growth inhibition and migration of human hepatoma HepG2 cell. It was well established that the signal transduction initiated by adhesion receptor in the cell surface contribute much to molecular mechanism of cell migration. Among the adhesion receptors, integrin is the most important. In our preliminary results, we found TPA may induce gene expression of integrin subtypes a2, a5, a6, b1 of HepG2 on both mRNA and cell surface protein level, which were dependent on PKC - and oxygen species (ROS) - mediated signaling. Furthermore, TPA can induce not only cell migration but also adhesion of HepG2. The TPA-induced cell adhesion and migration of HepG2 were enhanced when the cells were cultured on dishes coated with different extra-cellular matrixes including fibronectin and collagen I. This suggested that integrin-ECM interaction was involved in these processes. We further compare the difference of signal transduction between TPA-promoted migration and adhesion of HepG2. Our results demonstrated that activation of PKC, ERK, and the integrin-related signal kinase FAK and Src were transiently induced by TPA during cell adhesion but were sustainedly induced during migration induced by TPA in HepG2. This difference possibly relies on the different status of ROS-mediated signal transduction during these two cellular processes. On the one hand, TPA may trigger ROS-dependent PKC activation leading to sustained ERK activation and cell migration. On the other hand, the signal transduction for TPA-induced cell adhesion is ROS-independent, therefore the signal transduction is transient. Further studies, such as investigating whether ROS generation was induced during TPA-triggered cell migration but not cell adhesion of HepG2, will be needed to clarify these issues.