The CXCL12–CXCR4 axis promotes migration, invasiveness, and EMT in human papillary thyroid carcinoma B-CPAP cells via NF-κB signaling

Abstract

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy involving local and distant metastasis. It is known that CXC chemokine ligand 12 (CXCL12) interacts specifically with CXC chemokine receptor 4 (CXCR4) to guide the migration of PTC cells. However, the signaling pathway downstream of the CXCL12–CXCR4 axis in PTC is not fully understood. In the present study, high expression of CXCR4 was detected in 38 out of 82 specimens of PTC, and the expression level of CXCR4 significantly correlated with the stage of PTC. Additionally, the roles of the CXCL12–CXCR4 axis in the migration, invasion, and epithelial–mesenchymal transition (EMT) of B-CPAP cells were investigated in vitro. The motility and invasiveness were significantly enhanced in CXCR4-overexpressing B-CPAP cells with CXCL12 treatment. Moreover, the CXCL12–CXCR4 axis promoted the EMT process, as evidenced by a decreased level of E-cadherin and increased expressions of N-cadherin and vimentin. Furthermore, the CXCL12–CXCR4 axis activated the nuclear factor kappa-B (NF-κB) signaling pathway, whereas BAY11-7082, an IκB phosphorylation inhibitor, counteracted CXCL12–CXCR4-induced migration, invasion, and EMT processes in B-CPAP cells. In conclusion, the CXCL12–CXCR4 axis promotes the migration, invasion, and EMT processes in B-CPAP cells, at least partly, by activating the NF-κB signaling pathway.