ERBB3 binding protein 1 promotes the progression of malignant melanoma through activation of the Wnt/ β-catenin signaling pathway

Background: Malignant melanoma (MM) is highly metastatic and has the highest mortality rate in patients with skin cancer. The ERBB3 binding protein 1 (Ebp1) has been linked to the onset and progression of a number of malignancies. However, the role of Ebp1 in MM has not yet been reported.

Methods: Multiple databases were analyzed for comparing the expression of Ebp1 in normal skin and MM. Ebp1 expression was knocked down in A375 and B16 cells, and the impact of Ebp1 on the cell growth was tested by CCK-8, plate clone colony, and cell cycle assays. Scratch, transwell, and in vivo caudal vein lung metastasis tests were also used to confirm the effects of Ebp1 on melanoma cells migration, invasion, and metastasis. Furthermore, the possible molecular mechanism of Ebp1 was predicted by set enrichment analysis and verified by western blotting.

Results: Ebp1 expression was substantially higher in MM than it was in normal skin, and Ebp1 was linked to the clinical stage and lymph node metastases of patients with MM. Knockdown of Ebp1 inhibited cell proliferation, migration, and invasion. In vivo experiments further verified that the knockdown of Ebp1 had an obvious inhibitory effect on lung metastasis in nude mice. Knockdown of Ebp1 reduced vimentin, N-cadherin, slug, and snail expression while increasing E-cadherin expression. Furthermore, knockdown of Ebp1 reduced the expression of β-catenin, as well as its downstream targets CyclinD1 and p-GSK3β; however, a Wnt/β-catenin agonist could reverse this effect.

Conclusion: Ebp1 may promote the proliferation and metastasis of melanoma cells through activation of the Wnt/β-catenin pathway.