Decreasing Microtubule Actin Cross-Linking Factor 1 Inhibits Melanoma Metastasis by Decreasing Epithelial to Mesenchymal Transition

Xiaoying Wang, 1 Xiao Jian, 1 Jun Dou, 2 Zicheng Wei, 3 Fengshu Zhao 2 1Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China; 2Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3Department of Stomatology Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of ChinaCorrespondence: Jun Dou; Fengshu ZhaoDepartment of Pathogenic Biology and Immunology, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing 210009, People’s Republic of ChinaTel +86-25-83272454; +86-25-83272506Email njdoujun@seu.edu.cn; Fengshu_zhao@126.comBackground: The microtubule actin cross-linking factor 1 (MACF1) is involved in cellular migration, adhesion, and invasion processes. Its abnormal expression initiates tumor cell proliferation and metastasis in numerous cancer types.Methods: In this study, we utilized short hair-pin RNA interference of MACF1 to assess the inhibitory effects on the metastatic potential of B16F10 melanoma cells both in vitro and in vivo a mouse model.Results: The MACF1 expression was increased in B16F10 cells-induced tumor tissues; while the down-regulation of MACF1 impacted the B16F10 melanoma cell metastatic behavior by decreasing the ability of colony formation and invasion in vitro as well as inhibiting B16F10 cells-induced tumor growth and lung metastasis in vivo. The results of Western blot and immunohistochemistry indicated that the expression of E-cadherin and Smad-7 was significantly increased whereas the expression of N-cadherin and TGF-β 1 was significantly decreased in tumor tissue of mice challenged with the B16F10/MACF1-RNAi cells when compared with the B16F10 cells challenged mice.Conclusion: The data presented in this study demonstrated that down-regulated MACF1 expression decreased B16F10 melanoma metastasis in mice by inhibiting the epithelial to mesenchymal transition program. Thus, MACF1 may be a novel target for melanoma therapy.Keywords: melanoma, microtubule actin cross-linking factor 1, metastasis, epithelial to mesenchymal transition