Cell Surface GRP78, a New Paradigm in Signal Transduction Biology

Studies from Pizzo’s laboratory identified cell surface expression of the molecular chaperone GRP78 as a major factor in prostate cancer and other malignancies. Cell surface GRP78 functions as a signaling receptor promoting tumor proliferation and suppressing apoptosis. Patients with a number of malignancies mount an autoimmune response to GRP78 and these antibodies, which bind to the NH2 terminal domains of GRP78, are receptor agonists whose appearance is a marker of poor prognosis. More recently, his lab has shown that antibodies directed against the COOH-terminal domain of GRP78 are receptor antagonists which may have therapeutic potential for treating patients whose tumors express GRP78 on the cell surface.

• 1. Introduction to the Discovery of the Endoplasmic Reticulum Chaperone GRP78 on the Cell Surface2. The Endoplasmic Reticulum Chaperone GRP78 also Functions as a Cell Surface Signaling Receptor3. Cell surface GRP78: Anchoring and Translocation Mechanisms and Therapeutic Potential in Cancer4. Cell Surface GRP78: A Targetable Marker of Cancer Stem-like Cells5. Cell Surface GRP78 Regulates the Pro-Coagulant Activity of Tissue Factor 6. GRP78 Modulates the Plasminogen Activating System in the Brain: Implications for Human Disease7. Escherichia coli Subtilase Cleaves Cell Surface GRP78 preventing COOH-terminal Signaling