FBXW7 inhibits invasion, migration and angiogenesis in ovarian cancer cells by suppressing VEGF expression through inactivation of β-catenin signaling.
FBXW7 inhibits invasion, migration and angiogenesis in ovarian cancer cells by suppressing VEGF expression through inactivation of β-catenin signaling.
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DOI：
10.3892/etm.2021.9945
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发表时间：
2021-05
影响因子：
2.7
通讯作者：
Shen J
中科院分区：
文献类型：
--
作者：
Zhong L;Pan Y;Shen J
F-box 和 WD 重复结构域包含 7 (FBXW7) 是一种肿瘤抑制基因，在多种人类恶性肿瘤中经常失活。本研究旨在探讨FBXW7在卵巢癌（OC）细胞侵袭、迁移和血管生成中的作用，并确定其潜在的分子机制。首先，使用蛋白质印迹法检测了几种人 OC 细胞系中 FBXW7 和血管内皮生长因子 (VEGF) 的表达水平。随后，FBXW7 过表达以确定 SKOV3 细胞中 VEGF 的表达。转染 FBXW7 和 VEGF 过表达质粒后进行 Transwell、伤口愈合和管形成实验，分别评估 SKOV3 细胞的侵袭、迁移和血管生成。进行蛋白质印迹分析以检测上皮间质转化和血管生成相关蛋白的表达水平。此外，还评估了 β-catenin 和 c-Myc 的表达水平，并使用 β-catenin 信号传导激动剂氯化锂 (LiCl) 来阐明 FBXW7 在 OC 中介导其抗肿瘤活性的分子机制。结果表明，与正常卵巢细胞相比，OC细胞系中FBXW7表达显着下调，而VEGF表达显着上调。 FBXW7 的过表达显着降低 SKOV3 细胞中 VEGF 的表达。值得注意的是，VEGF的过表达逆转了FBXW7过表达对OC细胞侵袭、迁移和血管生成的抑制作用，伴随着N-cadherin、slug、CD31、VEGF受体1（VEGFR1）和VEGFR2的表达水平上调，以及E-cadherin的表达水平下调。此外，FBXW7的过表达显着抑制β-连环蛋白和c-Myc表达，而用LiCl处理SKOV3细胞后，FBXW7过表达后降低的VEGF、VEGFR1和VEGFR2表达水平增加。总体而言，本研究的结果表明，FBXW7 通过失活 β-catenin 信号传导抑制 VEGF 表达，从而抑制 OC 细胞的侵袭、迁移和血管生成。因此，FBXW7可作为治疗OC的新治疗靶点。
F-box and WD repeat domain containing 7 (FBXW7) is a tumor suppressor gene frequently inactivated in several human malignancies. The present study aimed to investigate the role of FBXW7 in the invasion, migration and angiogenesis of ovarian cancer (OC) cells, and to identify its potential molecular mechanisms. First, the expression levels of FBXW7 and vascular endothelial growth factor (VEGF) were detected in several human OC cell lines using western blotting. Subsequently, FBXW7 was overexpressed to determine VEGF expression in SKOV3 cells. Transwell, wound healing and tube formation assays were performed following transfection with FBXW7 and VEGF overexpression plasmids to assess invasion, migration and angiogenesis in SKOV3 cells, respectively. Western blot analysis was performed to detect the expression levels of epithelial-to-mesenchymal transition and angiogenesis-associated proteins. In addition, the expression levels of β-catenin and c-Myc were assessed, and lithium chloride (LiCl), an agonist of β-catenin signaling, was used to elucidate the molecular mechanisms by which FBXW7 mediates its antitumor activity in OC. The results demonstrated that FBXW7 expression was markedly downregulated, whilst VEGF expression was markedly upregulated in OC cell lines compared with that in normal ovarian cells. Overexpression of FBXW7 significantly decreased VEGF expression in SKOV3 cells. Notably, overexpression of VEGF reversed the inhibitory effects of FBXW7 overexpression on the invasion, migration and angiogenesis of OC cells, accompanied by upregulated expression levels of N-cadherin, slug, CD31, VEGF receptor 1 (VEGFR1) and VEGFR2, and downregulated expression levels of E-cadherin. Furthermore, overexpression of FBXW7 markedly suppressed β-catenin and c-Myc expression, whereas the decreased expression levels of VEGF, VEGFR1 and VEGFR2 following overexpression of FBXW7 were increased after treatment of SKOV3 cells with LiCl. Overall, the results of the present study suggested that FBXW7 inhibited invasion, migration and angiogenesis of OC cells by suppressing VEGF expression through inactivation of β-catenin signaling. Thus, FBXW7 may be used as a novel therapeutic target for the treatment of OC.
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影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
VEGF通过调节鼻咽癌EMT和MMPs促进迁移和侵袭
影响因子：
3.9
作者：
Chen L;Lin G;Chen K;Liang R;Wan F;Zhang C;Tian G;Zhu X
通讯作者：
Zhu X
DOI：
10.18632/aging.103824
发表时间：
2020-09-07
期刊：
Aging
影响因子：
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作者：
Peng Y;Li Y;Li Y;Wu A;Fan L;Huang W;Fu C;Deng Z;Wang K;Zhang Y;Shu G;Yin G
通讯作者：
Yin G
DOI：
10.1016/j.bbagen.2018.08.013
发表时间：
2018-12-01
影响因子：
3
作者：
Sadremomtaz, Afsaneh;Mansouri, Kamran;Asghari, S. Mohsen
通讯作者：
Asghari, S. Mohsen
影响因子：
7.4
作者：
Dai, Jun;Wei, Rujia;Kong, Beihua
通讯作者：
Kong, Beihua