The role of Eps8 in macrophage-stimulated colon cancer cell migration

• Main Authors: Yu-ChenPan, 潘郁辰
• Other Authors: Tzeng-Horng Leu
• Format: Others
• Language: en_US
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/35980832160161234604

碩士 === 國立成功大學 === 藥理學研究所 === 102 === Macrophages in tumor microenvironment affects cancer development and progression. Previous study indicated that Eps8 participated in LPS-induced phagocytosis in macrophages. Given that abnormal expression of Eps8 contributes to the malignancy of various types of cancer, we want to address the importance of Eps8 in promoting cancer progression. Accompanying with THP-1 differentiating from monocytes into macrophages, the expressions of Eps8 as well as Src kinase activity are elevated. LPS treatment further elevates their expression. Attenuation of Eps8 abolished cell spreading and phagocytic activity in LPS- treated THP-1 macrophages. Thus, like in RAW264.7 cells, Eps8 plays an important role in the innate immunity in human macrophages. Interestingly, we discovered that silencing Eps8 in THP-1 macrophage reduced cell motility in both SW480 and THP-1 cells under co-cultured condition. Besides, THP-1-derived conditioned medium enhanced the cell motility in SW480 cells while silencing Eps8 in THP-1 cells abolished this effect. Similar phenomenon was observed in hypoxia condition. Western blotting indicates Eps8 participates in the activation of FAK and Src activity under hypoxia condition. These findings reveal that Eps8 might involve in macrophages promoting colon cancer progression.