Migration and invasion of
tumor cells are essential prerequisites for the formation of
metastasis in malignant diseases. Previously, we have reported that
CC chemokine receptor 7 (CCR7) regulates the mobility of
squamous cell carcinoma of head and neck (SCCHN) cells through several pathways, such as
integrin and cdc42. In this study, we investigated the connection between CCR7 and
mitogen-activated protein kinase (MAPK) family members, and their influence on cell invasion and migration in metastatic SCCHN cells. Western blotting, immunostaining and fluorescence microcopy were used to detect the
protein expression and distribution of MAPKs, and the Migration assay,
Matrigel invasion assay and wound-healing assay to detect the role of MAPKs in CCR7 regulating cell mobility. To analyze the correlation between CCR7 and MAPK activity and clinicopathological factors immunohistochemical staining was emplyed. The results showed stimulation of CCL19 and the activation of CCR7 could induce ERK1/2 and JNK phosphorylation, while it had no efect on p38. After activation, ERK1/2 and JNK promoted
E-cadherin low expression and
Vimentin high expression. The MAPK pathway not only mediated CCR7 induced cell migration, but also mediated invasion speed. The immunohistochemistry results showed that CCR7 was correlated with the phosphorylation of ERK1/2 and JNK in SCCHN, and these molecules were all associated with
lymph node metastasis. Therefore, our study demonstrates that MAPK members (ERK1/2 and JNK) play a key role in CCR7 regulating SCCHN
metastasis.