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IKKe coordinates invasion and metastasis

ABSTRACT: IKKe was identified previously as a breast cancer oncogene and was associated with poor clinical outcome in ovarian cancer. In order to elucidate functional roles of IKKe, we used microarray analysis to identify genes changed upon IKKe shRNA knockdown and compared with genes affected in ovarian cancers

ORGANISM(S): Homo sapiens

PROVIDER: GSE42320 | GEO | 2012/11/16

SECONDARY ACCESSION(S): PRJNA181022

REPOSITORIES: GEO

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IKKe coordinates invasion and metastasis

Project description:IKKe was identified previously as a breast cancer oncogene and was associated with poor clinical outcome in ovarian cancer. In order to elucidate functional roles of IKKe, we used microarray analysis to identify genes changed upon IKKe shRNA knockdown and compared with genes affected in ovarian cancers IKKe was knockdowned by 2 different IKKe shRNAs in Ovcar5 in 6 replicates and candidate downstream targets were selected if changed by both shRNAs

2012-11-16 | E-GEOD-42320 | biostudies-arrayexpress

IKKe coordinates invasion and metastasis

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Comparison between MCF7-IKKe overexpressing cells and MCF7 control cells

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Expression data from wild type (wt) and Ikbke knockout (Ikke) embryonic fibroblasts (EF)

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Knock down of LIMD2 inhibits the invasion and metastasis of ovarian cancer

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Project description:Inhibitor of IκB kinases (IKK) are key regulators of NF-κB signaling. Three IKK isoforms-α, β, and ε-have been linked to oncogenesis, yet the precise components of NF-κB signaling in ovarian cancer have not yet been dissected. We surveyed 120 ovarian cancer specimens for IKK-ε expression. Notably, cytoplasmic expression was elevated in metastatic lesions relative to primary tumors (P = 0.03). Therefore, we hypothesized that IKK-ε drives ovarian cancer metastasis. IKK-ε was identified previously as a breast cancer oncogene and was associated with poor clinical outcome in ovarian cancer. We now define an ovarian cancer-specific IKK-ε-regulated gene expression signature using stably expressed short hairpin RNA targeting IKK-ε. Pathway analysis of the signature indicated that IKK-ε regulates expression of genes involved in cell motility and inflammation. We further showed that IKK-ε depletion in metastatic ovarian cancer cell lines decreased growth, adhesion, and invasion. Consistently, human xenografts depleted of IKK-ε in mice showed decreased aggressiveness, whereas overexpression of IKK-ε in a less invasive ovarian cancer cell line increased metastasis in vivo. Taken together, these data provide evidence that IKK-ε is a key coordinator of invasion and metastasis programs in ovarian cancer. Inhibition of IKK-ε signaling thus emerges as a viable therapeutic strategy in women whose ovarian cancer shows aberrant activation of this pathway.

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