title: Ikaros inhibits proliferation and, through upregulation of Slug, increases             metastatic ability of ovarian serous adenocarcinoma cells.
abstract: 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 G1 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 Snail1             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.
authors.affiliation: Department of Pathophysiology, Chemical Biology Division of Shanghai Universities E-Institutes, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
authors.forename: Li-Cai
authors.initials: LC
authors.lastname: He
authors.forename: Feng-Hou
authors.initials: FH
authors.lastname: Gao
authors.forename: Han-Zhang
authors.initials: HZ
authors.lastname: Xu
authors.forename: Shan
authors.initials: S
authors.lastname: Zhao
authors.forename: Chun-Min
authors.initials: CM
authors.lastname: Ma
authors.forename: June
authors.initials: J
authors.lastname: Li
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.forename: Ying-Li
authors.initials: YL
authors.lastname: Wu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000235:genetics; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D012016:Reference Values; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C497239:IKZF1 protein, human; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051740:Ikaros Transcription Factor