Ikaros inhibits proliferation and, through upregulation of Slug, increases metastatic ability of ovarian serous adenocarcinoma cells
Ikaros inhibits proliferation and, through upregulation of Slug, increases metastatic ability of ovarian serous adenocarcinoma cells
复制标题
Ikaros 抑制增殖，并通过上调 Slug 增加卵巢浆液性腺癌细胞的转移能力。
DOI：
10.3892/or.2012.1946
复制
发表时间：
2012-10-01
期刊：
影响因子：
4.2
通讯作者：
Wu, Ying-Li
中科院分区：
文献类型：
--
作者：
He, Li-Cai;Gao, Feng-Hou;Wu, Ying-Li
转录因子Ikaros最初被发现是淋巴细胞分化的关键调节因子。在本研究中，我们首次提供了Ikaros在卵巢癌组织中表达水平高于正常卵巢组织的证据，并与卵巢浆液性腺癌的高FIGO分期和低分化状态显著相关。为此，我们将IK1 （Ikaros全长）转染到SKOV3卵巢癌细胞系中，检测细胞的增殖、迁移和侵袭等生物学行为。我们发现IK1的过表达通过诱导G、阻滞抑制细胞增殖，同时伴有P27和P21的上调以及cyclin D1和D2的下调。另一方面，IK1增加了卵巢癌细胞的迁移和侵袭，通过划痕实验、跨井迁移实验和侵袭实验进行了评估。过表达IK1显著增加了Slug的mRNA和蛋白表达，而snail的mRNA和蛋白表达水平未见提高。同时下调和上调了Slug参与迁移的靶基因E-cadherin和MMP-2。此外，敲除Slug可消除ik1介导的迁移和侵袭增加。这些数据表明，Slug在ik1诱导的迁移和侵袭中起重要作用。总之，我们首次发现IK1在卵巢癌细胞的增殖、迁移和侵袭中起双重作用，为卵巢癌细胞的转移提供了新的认识。
The transcription factor Ikaros was originally found to function as a key regulator of lymphocyte differentiation. In this study, we provide the first evidence that Ikaros is expressed at higher levels in ovarian cancer tissues compared with normal ovarian tissues and is significantly associated with high FIGO stage and low differentiation state in ovarian serous adenocarcinoma. To this end, we transfected IK1 (full length of Ikaros) into the SKOV3 ovarian cancer cell line and examined cell biological behaviors including proliferation, migration and invasion. We found that overexpression of IK1 inhibited cell proliferation by inducing G, arrest, accompanied by the upregulation of P27 and P21 and downregulation of cyclin D1 and D2. On the other hand, IK1 increased the migration and invasion of ovarian cancer cells, as assessed by scratch-wound assay, transwell migration assay, and invasion assay. Overexpression of IK1 significantly increased Slug but not Snaill expression at both mRNA and protein levels. It also downregulated and upregulated E-cadherin and MMP-2, two target genes of Slug involved in migration, respectively. Furthermore, knocking down Slug abrogated IK1-mediated increase in migration and invasion. These data suggest that Slug plays an important role in IK1-induced migration and invasion. In conclusion, we show for the first time that IK1 plays a dual role in the proliferation, migration and invasion of ovarian cancer cells, providing new insights into their metastasis.