Journal
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volume 45, Issue 5, Pages 987-994Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2013.02.002
Keywords
GRP78; Colorectal cancer; Migration; Invasion; uPA
Categories
Funding
- National Natural Science Foundation of China [31201072, 31271516, 81150026]
- Shanxi Scholarship Council of China
- Shanxi Province Science Foundation for Youths [2012021028-4]
- Research Fund for the Doctoral Program of Higher Education of China [20111401110011]
- Shanxi International Cooperation Project [2011081058]
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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 beta 1-integrin and was involved in cell-matrix adhesion through regulation of focal adhesion kinase (FAR). 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. (C) 2013 Elsevier Ltd. All rights reserved.
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