surface GRP78 promoted the secretion and activity ofMMP-
2. Our results suggested that MMP-2 lies downstream of specific
signaling molecule and regulated tumor invasion independently
or in combination with MMP-9 by degrading the
extracellularmatrix.Many publications have obtained similar
results. For example, Stat3 activation specifically regulates
MMP-2 and promotes the invasion of melanoma. S100A14
protein, amember of EF-hand calcium-binding proteins subfamily,
enhances the expression of MMP-2 and, therefore,
promotes the motility of colon cancer cells.
Finally, EMT plays essential roles in the initiation of cancer
cell invasion. Many data have reported that EMT is perquisite
for the invasion of cancer cells.We demonstrated that
the cell surface GRP78 regulates EMTprocess in hepatocellular
carcinoma cells. Inhibition of the endogenous cell surface
GRP78 decreased the invasive potential of hepatocellular carcinoma
cells. However, forced expression of exogenous cell
surface GRP78 enhanced the invasive potential of cancer
cells.
Taken together, the cell surface GRP78 plays a stimulatory
role in the invasion of hepatocellular carcinoma cells.Thecell
surface GRP78 induced the invasion of cancer cells by enhancing
the activity of MMP-2 and regulating EMT process.
Our results suggest that GRP78 on the cell surface may be a
potential target for inhibiting clinically the invasion of hepatocellular
carcinoma cells.