Study on the Mechanism How Cell Attachment-induced Activation of Met and EGFR in A431 Cells
碩士 === 國立中興大學 === 生物醫學研究所 === 99 === Overexpression of growth factor receptors often leads to their activation in a ligand-independent manner. In this study, I demonstrate that the hepatocyte growth factor receptor Met and epidermal growth factor receptor (EGFR) are constitutively activated in human...
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ndltd-TW-099NCHU51140172017-10-29T04:34:12Z http://ndltd.ncl.edu.tw/handle/71508642141288618787 Study on the Mechanism How Cell Attachment-induced Activation of Met and EGFR in A431 Cells 探討在A431細胞中細胞貼附引起Met與EGFR活化的機轉 Ying-Che Lu 呂瑛哲 碩士 國立中興大學 生物醫學研究所 99 Overexpression of growth factor receptors often leads to their activation in a ligand-independent manner. In this study, I demonstrate that the hepatocyte growth factor receptor Met and epidermal growth factor receptor (EGFR) are constitutively activated in human epidermal carcinoma A431 cells, which confers proliferative and invasive potentials to the cells. The ligand-independent activation of Met and EGFR in A431 cells relies on cell attachment to a substratum, but is independent of cell spreading, extracellular matrix proteins, and substratum stiffness. This cell attachment-induced activation of Met and EGFR cannot be attributed to Src activation, production of reactive oxygen species, and the integrity of the cytoskeleton. In addition, I demonstrate that Met and EGFR are independently activated upon cell attachment. However, partial depletion of Met and EGFR prevents their activation upon cell adhesion, suggesting that overexpression of the receptors is a prerequisite for their self-activation upon cell attachment. Moreover, I discover that the distribution of lipid rafts is limited at the area of basal surface when cells are replated. Disruption of lipid rafts by depletion of membrane cholesterol with methyl-beta-cyclodextrin impairs Met activation, but enhances EGFR activation upon cell attachment. Although the majority of both active Met and EGFR are detected in the 0.04% Triton-soluble fractions (i.e. non-raft fraction), disturbance of lipid rafts by methyl-beta-cyclodextrin has opposite impacts to Met and EGFR. Therefore, it is possible that lipid rafts are involved in regulation of attachment-induced activation of Met and EGFR in A431 cells. Hong-Chen Chen 陳鴻震 2011 學位論文 ; thesis 75 zh-TW |
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碩士 === 國立中興大學 === 生物醫學研究所 === 99 === Overexpression of growth factor receptors often leads to their activation in a ligand-independent manner. In this study, I demonstrate that the hepatocyte growth factor receptor Met and epidermal growth factor receptor (EGFR) are constitutively activated in human epidermal carcinoma A431 cells, which confers proliferative and invasive potentials to the cells. The ligand-independent activation of Met and EGFR in A431 cells relies on cell attachment to a substratum, but is independent of cell spreading, extracellular matrix proteins, and substratum stiffness. This cell attachment-induced activation of Met and EGFR cannot be attributed to Src activation, production of reactive oxygen species, and the integrity of the cytoskeleton. In addition, I demonstrate that Met and EGFR are independently activated upon cell attachment. However, partial depletion of Met and EGFR prevents their activation upon cell adhesion, suggesting that overexpression of the receptors is a prerequisite for their self-activation upon cell attachment. Moreover, I discover that the distribution of lipid rafts is limited at the area of basal surface when cells are replated. Disruption of lipid rafts by depletion of membrane cholesterol with methyl-beta-cyclodextrin impairs Met activation, but enhances EGFR activation upon cell attachment. Although the majority of both active Met and EGFR are detected in the 0.04% Triton-soluble fractions (i.e. non-raft fraction), disturbance of lipid rafts by methyl-beta-cyclodextrin has opposite impacts to Met and EGFR. Therefore, it is possible that lipid rafts are involved in regulation of attachment-induced activation of Met and EGFR in A431 cells.
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Hong-Chen Chen |
author_facet |
Hong-Chen Chen Ying-Che Lu 呂瑛哲 |
author |
Ying-Che Lu 呂瑛哲 |
spellingShingle |
Ying-Che Lu 呂瑛哲 Study on the Mechanism How Cell Attachment-induced Activation of Met and EGFR in A431 Cells |
author_sort |
Ying-Che Lu |
title |
Study on the Mechanism How Cell Attachment-induced Activation of Met and EGFR in A431 Cells |
title_short |
Study on the Mechanism How Cell Attachment-induced Activation of Met and EGFR in A431 Cells |
title_full |
Study on the Mechanism How Cell Attachment-induced Activation of Met and EGFR in A431 Cells |
title_fullStr |
Study on the Mechanism How Cell Attachment-induced Activation of Met and EGFR in A431 Cells |
title_full_unstemmed |
Study on the Mechanism How Cell Attachment-induced Activation of Met and EGFR in A431 Cells |
title_sort |
study on the mechanism how cell attachment-induced activation of met and egfr in a431 cells |
publishDate |
2011 |
url |
http://ndltd.ncl.edu.tw/handle/71508642141288618787 |
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