Journal
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
Volume 16, Issue 4, Pages 529-536Publisher
IVYSPRING INT PUBL
DOI: 10.7150/ijms.27401
Keywords
protein 4.1B; melanoma; migration; epithelial-mesenchymal transition (EMT)
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Funding
- National Natural Science Foundation of China [81602 537, 81571526, 8167154]
- Natural Science Foundation of Henan Province of China [162300410277]
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Epithelial-mesenchymal transition (EMT), which involves the dramatic reorganization of the cytoskeleton, is a crucial initiating step in tumor invasion and metastasis. Protein 4.1 B is a membrane-cytoskeleton cross-linker that plays an important role in tumor progression and metastasis; however, the functional roles of 4.1 B in melanoma remain unclear. In this study, we aimed to investigate the effect and underlying mechanism of 4.1 B on melanoma cells. Our results demonstrated that 4.1B expression was downregulated in murine B16 and B16-F10 melanoma cell lines. Ectopic 4.1 B expression significantly inhibited the migration of melanoma cells and pulmonary metastasis. We further investigated the possible mechanism underlying the effect of 4.1 B on EMT. The results showed that ectopic 4.1 B 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 alpha 5, beta 3 and matrix metalloproteinase 9 (MMP-9), which is known to regulate cell adhesion, migration and invasion, were suppressed. In conclusion, our data indicate that 4.1 B is an important regulator during EMT progression in melanoma cells, which may present a potential target for the prevention and treatment of melanoma.
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