Protein 4.1B Suppresses Tumor Metastasis by Regulating Epithelial-mesenchymal Transition Progression in Melanoma Cells

Chengbo Wang^1*, Keyan Li^1*, Yingli Men^3*, Cong Ding¹, Juan Du¹, Taotao Liang¹, Zhenyu Ji², Lixiang Chen¹, Ting Wang^1✉, Qiaozhen Kang^1✉

1. School of Life Sciences, Zhengzhou University, No. 100 Science Avenue, Zhengzhou 450001, P.R. China
2. Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, 40 University Road, Zhengzhou 450052, P.R. China
3. Translational medical center, People's Hospital of Zhengzhou, 33 Huanghe Road, Zhengzhou 450003, P.R.China
*The authors contributed equally to this work.

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Citation:
Wang C, Li K, Men Y, Ding C, Du J, Liang T, Ji Z, Chen L, Wang T, Kang Q. Protein 4.1B Suppresses Tumor Metastasis by Regulating Epithelial-mesenchymal Transition Progression in Melanoma Cells. Int J Med Sci 2019; 16(4):529-536. doi:10.7150/ijms.27401. Available from http://www.medsci.org/v16p0529.htm

Abstract

Epithelial-mesenchymal transition (EMT), which involves the dramatic reorganization of the cytoskeleton, is a crucial initiating step in tumor invasion and metastasis. Protein 4.1B is a membrane-cytoskeleton cross-linker that plays an important role in tumor progression and metastasis; however, the functional roles of 4.1B in melanoma remain unclear. In this study, we aimed to investigate the effect and underlying mechanism of 4.1B on melanoma cells. Our results demonstrated that 4.1B expression was downregulated in murine B16 and B16-F10 melanoma cell lines. Ectopic 4.1B expression significantly inhibited the migration of melanoma cells and pulmonary metastasis. We further investigated the possible mechanism underlying the effect of 4.1B on EMT. The results showed that ectopic 4.1B expression altered the expression of representative EMT markers (E-cadherin, vimentin and N-cadherin), and inhibited the expression of three important transcription factors (Slug, Snail, and Twist) related to EMT in melanoma cells. Moreover, the expression of integrin α5, β3 and matrix metalloproteinase 9 (MMP-9), which is known to regulate cell adhesion, migration and invasion, were suppressed. In conclusion, our data indicate that 4.1B is an important regulator during EMT progression in melanoma cells, which may present a potential target for the prevention and treatment of melanoma.

Keywords: protein 4.1B, melanoma, migration, epithelial-mesenchymal transition (EMT)