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V TABLE OF CONTENTS  VII LIST OF FIGURES  XI ABBREVIATIONS  XIV Introduction  1 1.1 Cancer Metastasis  1 1.1.1 Distant Metastasis is a Multi-Step Process  1 1.1.2 Circulating Tumor Cells (CTCs)  3 1.1.3 Extravasation  3 1.1.4 Metastasis of Breast Cancer  5 1.2 Hemodynamic Shear Stress  5 1.2.1 The Effects of Shear Stress on Endothelial Cells  6 1.2.2 The Effects of Shear Stress on Tumor Cells  7 1.3 Tumor Cell Migration  9 1.3.1 The Process of Cell Migration  9 1.3.2 ERK1/2 and Cell Migration  11 1.3.3 Tumor Cell Migration is Important for Metastasis  13 1.3.4 Tumor Cell Migration is Regulated by Extracellular Signals  14

The pro-metastatic effects of hemodynamic shear stress : breast cancer cells acquire aggressiveness during circulation