Front Cover

Cell Surface GRP78, a New Paradigm in Signal Transduction Biology

Copyright Page

Contents

List of Contributors

Preface

1 An Historical Perspective: Cell Surface GRP78, a New Paradigm in Signal Transduction Biology

Discovery of Cell Surface GRP78

GRP78 and Cancer Cell Biology

A Most Complex Signaling Mechanism

References

2 The Endoplasmic Reticulum Chaperone GRP78 Also Functions as a Cell Surface Signaling Receptor

Introduction

Release of CS-GRP78 Into the Extracellular Environment

Secreted GRP78

GRP78 in Exosomes

Induction of GRP78 to the Cell Surface

CS-GRP78 Ligands and Their Cellular Effects

CS-GRP78 Forms Complexes With a Variety of Cell-Surface Anchored Proteins

CS-GRP78 Controls Key Oncogenic Signaling Pathways

Biological Functions of CS-GRP78 in Cancer

Cell Survival and Proliferation

Apoptosis

Invasion and Migration

Transcriptional Activation

Metabolism

The Role of CS-GRP78 in Other Physiological Diseases

Angiogenesis

Virus Internalization

Inflammation and Immunity

Arthritis

Therapeutic Targeting of CS-GRP78

GRP78 Autoantibodies and Their Physiological Roles

Concluding Remarks

References

3 Cell Surface GRP78: Anchoring and Translocation Mechanisms and Therapeutic Potential in Cancer

Introduction

Anchoring on the Cell Surface

Cell Surface Anchoring of ER-Transmembrane Chaperones

Cell Surface Anchoring of Peripheral Proteins

CS-GRP78 Binding Ligands, Membrane Proteins and Functions

Translocation Mechanisms

Intrinsic Factors

Protein–Protein Interaction in GRP78 Translocation

Trafficking Routes

Therapeutic Potential in Cancer

Antibodies

Peptide Conjugates

Proapoptotic Ligands

Conclusions and Perspectives

References

4 Cell Surface GRP78: A Novel Regulator of Tissue Factor Procoagulant Activity

The 78 kDa Glucose-Regulated Protein (GRP78)

GRP78 Protein Structure

Translocation of GRP78 to the Cell Surface

Regulating the Levels of Cell Surface GRP78

Nonchaperone Functions of GRP78

Ca2+ Binding Protein

GRP78 and Pathology

Anti-GRP78 Autoantibodies and Cancer

GRP78 and the Coagulation System

Tissue Factor

The Role of Tissue Factor in Hemostasis

Tissue Factor Structure

Tissue Factor and Disease

Regulation of Tissue Factor Activity

Tissue Factor Dimerization

Altered Phospholipid Asymmetry

Tissue Factor Compartmentalization in Caveolae

Tissue Factor Disulfide Bond Isomerization

Regulation of Tissue Factor by Cell Surface GRP78

Implication of TF Activation via Cell Surface GRP78 in Cancer

Conclusion

References

5 Novel Cell Surface Targets for the Plasminogen Activating System in the Brain: Implications for Human Disease

Introduction

The Voltage-Dependent Anion Channel 1

Functions of Voltage-Dependent Anion Channel

The Plasminogen Activator System in the Brain

GRP78 and VDAC in the Brain

The Voltage-Dependent Anion Channel and Beta-Amyloid Peptides

Disorders Associated to Dysfunctions of the System Involving GRP78 and VDAC

VDAC as a Receptor of the Plasminogen Activator System in the Brain

References

6 Cell Surface GRP78: A Targetable Marker of Cancer Stem-Like Cells

Drug-Resistant, Growth-Arrested Tumor Cell Subpopulations Drive Tumor Recurrence

Epithelial–Mesenchymal Transition and Cancer Stemness

Glucose Regulated Protein of 78 kDa (GRP78), Stemness, and Therapy Resistance

Targeting Cell Surface GRP78 on Drug-Resistant Cancer Stem-Like Cells

Cancer Stem Cells and Their Transit Amplifying Progeny- Differences in Proliferative Potential

The One-Two Punch: Combination Therapies to Eliminate Therapy-Sensitive and Therapy-Resistant Tumor Cell Subpopulations

Are GRP78+ Stem-Like Cells Induced by Therapy or Enriched for by Therapy, and Why Do We Care?

Conclusions

References

7 Escherichia coli Subtilase Cleaves Cell Surface GRP78 Preventing COOH-Terminal Domain Signaling

GRP78

Subtilase

Subtilase as a Tool for Understanding GRP78 Functions

Unfolded Protein Response

Inflammation

Apoptosis

Cancer

Viruses

Cell Surface GRP78

Conclusions

References

Index

Back Cover