othesignalingmechanismsfordynamictraf ckingandturnoveroffocalad- sionproteinsinregulationoftractionandretractionforces,whichareneededfor celllocomotionandinvasion. Chapter9describestheinvolvementofNotchsign- ingpathwaywhichisnotonlyessentialforembryonicdevelopmentbutalsoplays importantroleintumorprogression. Chapter10reviewedtherecentlyidenti ed cancer- and metastasis-initiating cells involved in tumor progression. Especially, signal pathways that are frequently deregulated in cancer stem/progenitor cells v vi Preface duringcancerprogressionarehighlighted. Chapter11describestheroleoflipid rafts, a special component within membrane lipid domain, in signal transd- tion triggered by growth factor receptors leading to tumor metastasis. Finally, Chapters12,Chapters13,andChapters14presentthesignalingpathwaysresp- sibleformetastaticprogressionofspeci ctumorsincludingovariancancer,uveal melanomaandhepatoma,respectively. WethankallthecontributorsofeveryChapterinthebookincludingJia-RuWu, Chi-TanHu,LaureVoisin,StéphanieDuhamel,SylvainMeloche,AlexeyShiryaev, MarijkeVanGhelue,UgoMoens,AlessioGiubellino,PraveenR. Arany,Moulay A. Alaoui-Jamali, Krikor Bijian, Panagiota Toliopoulos, Pingyu Zhang, Patrick A. Zweidler-McKay,MurielleMimeault,SurinderK. Batra,SamirKumarPatra, LydiaW. T. Cheung,CarmanK. M. Ip,AliceS. T. Wong,CécileLaurent,Jérôme Couturier,XavierSastre-Garau,LaurenceDesjardins,EmmanuelBarillot,Sophie Piperno-Neumann,SimonSauleandRajagopalN. Aravalli. Wehopethisbookmightstimulatemorecancerbiologiststoemphasizethis eld whichbene tsdevisingmoreeffectivemoleculartargetingstrategiesforprevention ofcancermetastasis. Hualien,Taiwan Wen-ShengWu Chi-TanHu Contents 1 Overview of Signal Transduction in Tumor Metastasis. . . . . . . 1 Wen-ShengWuandJia-RuWu 2 Microenvironment Triggers EMT, Migration and Invasion of Primary Tumor via Multiple Signal Pathways . . . . . . . . . . 9 Wen-ShengWuandChi-TanHu 3 The ERK1/2 MAP Kinase Signaling Pathway in Tumor Progression and Metastas

Overview of Signal Transduction in Tumor Metastasis.- Microenvironment Triggers EMT, Migration and Invasion of Primary Tumor via Multiple Signal Pathways.- The ERK1/2 MAP Kinase Signaling Pathway in Tumor Progression and Metastasis.- Mitogen-Activated Protein Kinase-Activated Protein Kinases and Metastasis.- Grb2 and Other Adaptor Proteins in Tumor Metastasis.- The Role of ROS Signaling in Tumor Progression.- Signal Cross Talks for Sustained MAPK Activation and Cell Migration Mediated by Reactive Oxygen Species: The Involvement in Tumor Progression.- Insights into the Dynamics of Focal Adhesion Protein Trafficking in Invasive Cancer Cells and Clinical Implications.- Notch Signaling in Cancer Metastasis.- New Concepts on the Critical Functions of Cancer- and Metastasis-Initiating Cells in Treatment Resistance and Disease Relapse: Molecular Mechanisms, Signaling Transduction Elements and Novel Targeting Therapies.- Involvement of Lipid Rafts in Growth Factor Receptors-Mediated Signaling for Cancer Metastasis.- Cadherin-Catenin Signaling in Ovarian Cancer Progression.- PTP4A3, a Signal Molecule Deregulated in Uveal Melanoma Metastasis.- Signal Transduction Pathways Involved in Hepatocarcinogenesis and Metastasis of Hepatoma.