Cell-surface GRP78 facilitates colorectal cancer cell migration and invasion

Int J Biochem Cell Biol. 2013 May;45(5):987-94. doi: 10.1016/j.biocel.2013.02.002. Epub 2013 Feb 26.


Glucose regulated protein 78 (GRP78) is predominantly located in the endoplasmic reticulum as a molecular chaperone. It has also been found on the membranes of some cancer cells, acting as a receptor for a wide variety of ligands. However, its presence on colorectal cancer (CRC) cell surface and its role in CRC metastatic progression remain elusive. Here we reported that GRP78 was predominantly present in the form of clustering aggregates on CRC cell surfaces, and its surface abundance was strongly correlated with CRC differentiation stage. Interestingly, we observed that cell-surface GRP78 had an interaction with the ECM adhesion molecule β1-integrin and was involved in cell-matrix adhesion through regulation of focal adhesion kinase (FAK). Moreover, the present data also implicated that surface GRP78 promoted the cell invasion process, and this effect was at least partly mediated through its association with uPA-uPAR protease system. Together, our data suggests that surface GRP78 promotes CRC cell migration and invasion by regulating cell-matrix adhesion and ECM degradation, which is independent of its signaling receptor function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / physiology
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cell Movement / physiology*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Endoplasmic Reticulum Chaperone BiP
  • HT29 Cells
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Integrin beta1 / metabolism
  • Receptors, Urokinase Plasminogen Activator / metabolism
  • Signal Transduction


  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Integrin beta1
  • Receptors, Urokinase Plasminogen Activator