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

ERBB3 binding protein 1 promotes the progression of malignant melanoma through activation of the Wnt/ β-catenin signaling pathway.
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ERBB3 结合蛋白 1 通过激活 Wnt/β-catenin 信号通路促进恶性黑色素瘤的进展

DOI:
10.1186/s12935-022-02473-6
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发表时间:
2022-01-29
影响因子:
5.8
通讯作者:
Liu L
Liu L
中科院分区:
医学2区
文献类型:
--
作者:
Bao Y;Cui J;Yue Y;Cao S;Li X;Liu L

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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。ERBB 3结合蛋白1(Ebp 1)与许多恶性肿瘤的发生和进展有关。然而,Ebp 1在MM中的作用尚未报道。通过CCK-8法、平板克隆集落法和细胞周期法检测Ebp 1在A375和B16细胞中的表达,并分析Ebp 1对细胞生长的影响。Scratch、transwell和体内尾静脉肺转移试验也用于证实Ebp 1对黑色素瘤细胞迁移、侵袭和转移的影响。同时,通过集合富集分析预测了Ebp 1的可能作用机制,并通过Western blotting进行了验证。Ebp 1在MM中的表达显著高于正常皮肤,并且Ebp 1与MM患者的临床分期和淋巴结转移有关。Ebp 1的敲低抑制细胞增殖、迁移和侵袭。体内实验进一步验证了Ebp 1基因敲减对裸鼠肺转移有明显的抑制作用。Ebp 1的敲除降低了波形蛋白、N-钙粘蛋白、蛞蝓和蜗牛的表达,同时增加了E-钙粘蛋白的表达。此外,Ebp 1的敲低降低了β-catenin及其下游靶点CyclinD 1和p-GSK 3 β的表达;然而,Wnt/β-catenin激动剂可以逆转这种作用。Ebp 1可能通过激活Wnt/β-catenin通路促进黑色素瘤细胞的增殖和转移。
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.
DOI: 10.1038/s41388-018-0226-z
发表时间: 2018-07
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