Farmakovskaya M, Khromova N, Rybko V, Dugina V, Kopnin B, Kopnin P
a Blokhin Russian Cancer Research Center , Moscow , Russia.
b Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University , Moscow , Russia.
Cell Cycle. 2016;15(8):1084-92. doi: 10.1080/15384101.2016.1156268.
Here we show that cancer stem cells amount in human lung adenocarcinoma cell line A549 depends on E-cadherin expression. In fact, downregulation of E-cadherin expression enhanced expression of pluripotent genes (c-MYC, NESTIN, OCT3/4 and SOX2) and enriched cell population with the cells possessing the properties of so-called 'cancer stem cells' via activation of Wnt/β-catenin signaling. Repression of E-cadherin also stimulated cell proliferation and migration in vitro, decreased cell amount essential for xenografts formation in nude mice, increased tumors vascularization and growth. On the other hand, E-cadherin upregulation caused opposite effects i.e. diminished the number of cancer stem cells, decreased xenograft vascularization and decelerated tumor growth. Therefore, agents restoring E-cadherin expression may be useful in anticancer therapy.
在此我们表明，人肺腺癌细胞系A549中癌症干细胞的数量取决于E-钙黏蛋白的表达。事实上，E-钙黏蛋白表达的下调增强了多能基因（c-MYC、巢蛋白、OCT3/4和SOX2）的表达，并通过激活Wnt/β-连环蛋白信号通路，使具有所谓“癌症干细胞”特性的细胞群体富集。E-钙黏蛋白的抑制还刺激了体外细胞增殖和迁移，减少了裸鼠异种移植瘤形成所需的细胞数量，增加了肿瘤血管生成和生长。另一方面，E-钙黏蛋白的上调产生了相反的效果，即减少了癌症干细胞的数量，降低了异种移植瘤的血管生成并减缓了肿瘤生长。因此，恢复E-钙黏蛋白表达的药物可能在抗癌治疗中有用。
