SFRP5 inhibits the migration and invasion of melanoma cells through Wnt signaling pathway

Yangmei Chen,¹ Daopei Zou,¹ Nan Wang,² Tao Tan,² Yu Liu,¹ Qing Zhao,¹ Yihuan Pu,¹ Rabin Jung Thapa,¹ Jin Chen<sup>1

1</sup>Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China; ²Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China

Background: Secreted frizzled-related protein 5 (SFRP5) plays a key role in the development and progression of multiple tumors. However, the role and underlying mechanisms of SFRP5 in melanoma cells remain unknown.
Materials and methods: We used immunohistochemistry and Western blot analysis to detect the expression of SFRP5 in melanoma tissues and melanoma cells, respectively. Furthermore, both in vitro and in vivo assays were used to determine the effect of SFRP5 on malignant behavior in melanoma cells.
Results: We found that SFRP5 was markedly downregulated in melanoma tissues and cell lines. The SFRP5 overexpression exhibited no effect on the proliferation and apoptosis of melanoma cells but markedly suppressed the migration and invasion of melanoma cells in vitro. Regarding mechanisms, the SFRP5 overexpression inhibited the migration and invasion of melanoma cells by suppressing the epithelial–mesenchymal transition process and decreasing the matrix metalloproteinase-2/9 expression through the Wnt signaling pathway. Finally, in a xenograft animal model, we illustrated that the SFRP5 overexpression suppressed the tumor growth by decreasing angiogenesis and declined lung metastasis.
Conclusion: This study suggests that SFRP5 expression could be potentially useful in the invasion and metastasis of melanoma and serve as a putative promising target for human melanoma therapy.

Keywords: SFRP5, Wnt signaling, melanoma, migration, invasion