Tumor malignancy is associated with several features such as proliferation ability and frequency of
metastasis.
Osteopontin (OPN), which is abundantly expressed in bone matrix, is involved in cell adhesion, migration, invasion and cell proliferation via interaction with its receptor,
alphavbeta3 integrin. However, the effect of OPN on migration activity in human
lung cancer cells is mostly unknown. Here we found that OPN increased the migration via activation of
alphavbeta3 integrin in human
lung cancer cells (A549 cells).
Phosphatidylinositol 3-kinase inhibitor (PI3K;
Ly294002), Akt inhibitor or ERK inhibitor (
PD98059) inhibited the OPN-induced increase in the migration of
lung cancer cells. OPN stimulation increased the phosphorylation of
focal adhesion kinase (FAK), p85 subunit of PI3K,
serine 473 of Akt and ERK. In addition, treatment of A549 cells with
NF-kappaB inhibitor (
PDTC) or IkappaB
protease inhibitor (
TPCK) inhibited OPN-induced migration of
lung cancer cells. Stimulation of A549 cells with OPN also induced
IkappaB kinase alpha/beta (
IKK alpha/beta) phosphorylation,
IkappaBalpha phosphorylation, p65 Ser(536) phosphorylation, and kappaB-
luciferase activity. The OPN-mediated increases in
IKK alpha/beta,
IkappaBalpha and p65 Ser(536) phosphorylation were inhibited by
Ly294002, Akt inhibitor and
PD98059. Co-transfection with FAK, p85, Akt and ERK mutants also reduced the OPN-induced kappaB-
luciferase activity. Taken together, these results suggest that OPN acts through
alphavbeta3 integrin, which in turn activates the FAK, PI3K, Akt, ERK and
NF-kappaB pathways, contributing to the migration of
lung cancer cells.