SLUG promotes invasion and metastasis of anaplastic thyroid cancer cells through repression of E-cadherin

Objective: Overexpression of SLUG has been implicated in promoting migration and invasion of many cancer cells, including anaplastic thyroid cancer (ATC) cells. Thus, targeted down-regulation of SLUG expression in ATC cells and determination of its implications would provide new treatment approaches for disease management. Methods: Small interfering RNA (siRNA) targeting SLUG (SLUG siRNA) was used to develop clonal derivatives of the ATC SW1736 cells. SLUG cDNA transfection was used to restore the SLUG expression in the SLUG siRNA transfected SW1736 cells. E-cadherin siRNA was used to inhibit E-cadherin expression in the SLUG siRNA transfected SW1736 cells. The effect of SLUG and E-cadherin expression on migration and invasion of SW1736 cells in vitro was detected. Further, the effect of targeting SLUG on lung metastasis in an mouse SW1736 cell tumor model was detected. Results: Targeting SLUG expression by SLUG siRNA transfection in SW1736 cells showed a 75% decrease in migration and a 85% decrease in invasion in vitro. Targeting E-cadherin by E-cadherin siRNA transfection or SLUG overexpression by SLUG cDNA transfection restored the invasion and migration ability of SW1736 cells. In vivo analysis indicated a 80% decrease in the number of mice bearing macroscopic lung metastases. Analysis of SLUG signaling pathways in the clonal derivatives showed a decrease in SLUG expression and increase in E-cadherin expression in the SLUG siRNA transfected tumor. Conclusions: Therapies targeting SLUG signaling pathway may be more effective in preventing organ metastasis.