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Focal adhesion kinase (FAK) is involved in tumor cell migration and metastasis. However, the underlying mechanism remains unclear. Here, we present a signaling pathway involved in the regulation of melanoma cell migration by FAK. We found that the interference of FAK expression suppressed B16F10 cell migration/metastasis, and altered the expressions of genes involved in melanoma migration/metastasis. The down-regulation of FAK inhibited the expression of p-SrcY416, p-ERK1/2, Stat3 and p-Stat3Y705, while promoted the expression of PPARγ, miR-125b and E-cadherin. Then we found that FAK inhibited E-cadherin expression via p-SrcY416/p-ERK1/2/ p-Stat3Y705 and PPARγ/miR-125b/Stat3 signaling pathway in B16F10 cell. Moreover, miR-125b inhibited B16F10 cell migration. Furthermore, we repeated the key data with human melanoma cell line A375. The results obtained from A375 cells fell in line with those from B16F10 cells. Using Oncomine database, we found that the mRNA levels of FAK, Src, ERK1/2 and Stat3 increased, while the mRNA levels of PPARγ, C21orf34 (miR-125b host gene) and E-cadherin decreased in human metastatic melanoma. The data from human breast cancer confirmed those from metastatic melanoma.Taken together, our study suggests that down-regulation of FAK promotes E-cadherin expression via p-SrcY416/p-ERK1/2/p-Stat3Y705 and PPARγ/miR-125b/Stat3 signaling pathway. Our findings provide a novel explanation regarding how FAK promotes melanoma cell migration, suggesting that FAK might be a potential target for melanoma therapy.

Focal adhesion kinase (FAK) is a non‑receptor tyrosine kinase involved in the development and progression of cancer. However, the regulatory role of FAK in cell migration remains unclear. The aim of the present study was to investigate the mechanism underlying the regulation of melanoma cell migration by FAK. The effect of FAK knockdown on gene expression in B16F10 cells was examined by gene chip analysis. The expression levels of coiled‑coil domain containing 80 (CCDC80) and epithelial (E)‑cadherin were analyzed by reverse transcription quantitative polymerase chain reaction and western blotting. Wound healing and transwell assays were used to monitor B16F10 cell migration. It was identified that the knockdown of FAK increased the expression levels of CCDC80 and E‑cadherin, while the overexpression of CCDC80 elevated E‑cadherin expression. Concurrently, upregulation of CCDC80 inhibited the migration of B16F10 cells, and downregulation of CCDC80 promoted the migration of B16F10 cells. The clinical data from the Oncomine database also revealed that the mRNA level of FAK was increased while the mRNA levels of CCDC80 and E‑cadherin were decreased in patients with melanoma compared with normal controls. Taken together, the results of the present study suggest that the regulation of B16F10 melanoma cell migration by FAK is potentially mediated by CCDC80. [ABSTRACT FROM AUTHOR]