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GEP100 Mediated Cancer Cell Migration Driven by Epidermal Growth Factor-stimulated ERK1/2-Rac1 Signaling

Author: HuZhenZhen
Tutor: GuLuo
School: Nanjing Medical University
Course: Physiology
Keywords: Epidermal growth factor Cell migration Extracellular signal-regulated kinase Guanine nucleotide exchange protein 100 Urokinase-type plasminogen activator receptor Ras-related C3 botulinum toxin substrate 1
CLC: R730.2
Type: Master's thesis
Year: 2011
Downloads: 40
Quote: 0
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Abstract


Previous studies have shown , EGF inducible factor , EGF plays a key role of chemokines in human malignant cell migration process by GEP100 starting downstream signal . The other hand , GEP100 involved in the regulation of cell migration associated cell - matrix adhesion and cytoskeleton reconstruction , but GEP100 molecular mechanisms of malignant cell migration is unclear . This study on the basis of the establishment of in vitro EGF-induced MDA-MB-231 breast cancer cells and HepG2 hepatoma cell migration model to study the the signal path GEP100, Arf6 and ERK1/2-uPAR-Rac1 EGF-induced MDA-MB-231 breast cancer cells and HepG2 hepatoma cell migration in the role and the role of possible mechanisms , in order to provide a theoretical basis for elucidating the malignant tumor invasion and metastasis mechanism . The study found that : 1, GEP100 regulation of EGF -induced MDA-MB-231 breast cancer cells and HepG2 hepatoma cell migration . 2 , respectively, using the specific chemical blocker pretreatment of the cells , or transiently transfected Arf6 and Rac1 dominant negative mutation Arf6-T27N and Rac1-T17N plasmid or siRNA interference uPAR expression by cell scratch experiments confirmed GEP100 , Arf6, ERK1 / 2, uPAR and Rac1 in EGF-induced tumor cell migration . 3, because EGF could induced ERK1 / 2 activation and Rac1 and uPAR expression , transient transfection GEP100 PH domain deletion mutant (GEP100-ΔPH) can effectively inhibit EGF induced ERK1 / 2 and Rac1 activation and uPAR expression of ERK1 / 2 specific inhibitor U0126 and siRNA interference uPAR can significantly reduce the level of Rac1 activation results prove that the EGF induced MDA-MB-231 breast cancer cells and HepG2 cells migrate there GEP100 → Arf6 → ERK1 / 2 → uPAR → Rac1 signal regulatory pathways . 4, in the nude mouse model , GEP100 PH domain deletion mutant (GEP100-ΔPH) can significantly reduce the transfer capacity of MDA-MB-231 breast cancer cells in nude mice . In summary, we found for the first time GEP100-Arf6 the regulation of ERK1/2-uPAR-Rac1 signaling pathway intermediary EGF - induced MDA-MB-231 breast cancer cells and HepG2 hepatoma cell migration .

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CLC: > Medicine, health > Oncology > General issues > Tumor pathology, etiology
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