Bao Yanqiu, Cui Jingshu, Yue Yuyang, Cao Shuxia, Li Xiangdan, Liu Lan
Department of Dermatology, Yanbian University Hospital, Jilin, 133000, China.
Department of Pathology, Yanbian University Hospital, Jilin, 133000, China.
Cancer Cell Int. 2022 Jan 29;22(1):44. doi: 10.1186/s12935-022-02473-6.
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.
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.
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.
Ebp1 may promote the proliferation and metastasis of melanoma cells through activation of the Wnt/β-catenin pathway.
恶性黑色素瘤（MM）具有高度转移性，在皮肤癌患者中死亡率最高。ERBB3结合蛋白1（Ebp1）与多种恶性肿瘤的发生和发展有关。然而，Ebp1在MM中的作用尚未见报道。
分析多个数据库以比较Ebp1在正常皮肤和MM中的表达。在A375和B16细胞中敲低Ebp1表达，并通过CCK-8、平板克隆集落和细胞周期检测来测试Ebp1对细胞生长的影响。划痕、Transwell和体内尾静脉肺转移试验也用于证实Ebp1对黑色素瘤细胞迁移、侵袭和转移的影响。此外，通过集富集分析预测Ebp1可能的分子机制，并通过蛋白质免疫印迹法进行验证。
Ebp1在MM中的表达明显高于正常皮肤，且Ebp1与MM患者的临床分期和淋巴结转移有关。敲低Ebp1可抑制细胞增殖、迁移和侵袭。体内实验进一步证实，敲低Ebp1对裸鼠肺转移有明显抑制作用。敲低Ebp1可降低波形蛋白、N-钙黏蛋白、Slug和Snail的表达，同时增加E-钙黏蛋白的表达。此外，敲低Ebp1可降低β-连环蛋白及其下游靶点细胞周期蛋白D1和磷酸化糖原合成酶激酶3β的表达；然而，Wnt/β-连环蛋白激动剂可逆转这种作用。
Ebp1可能通过激活Wnt/β-连环蛋白通路促进黑色素瘤细胞的增殖和转移。
