Transcriptomics,Genomics

Dataset Information

21

KLF17 is a negative regulator of epithelial-mesenchymal transition and metastasis in breast cancer


ABSTRACT: Metastasis is a complex multi-step process requiring the concerted action of many genes and is the primary cause of cancer deaths. Pathways that regulate metastasis enhancement and suppression both contribute to tumor dissemination process. In order to identify novel metastasis suppressors, we set up a forward genetic screen in a mouse model. We transduced a genome-wide RNAi library into the non-metastatic 168FARN breast cancer cell line, orthotopically transplanted the cells into mouse mammary fat pads, and then selected for cells that could metastasize to the lung and identified an RNAi for the KLF17 gene. Conversely, ectopic expression of KLF17 in highly metastatic 4T1 breast cancer cell line inhibited their ability to metastasize from the mammary fat pad to the lung. We showed that suppression of KLF17 expression promotes breast cancer cell invasion and epithelial-mesenchymal transition (EMT). We also showed that KLF17 functions by directly binding to the promoter of Id-1, a key metastasis regulator in breast cancer, to inhibit its transcription. Finally, we demonstrated that KLF17 expression is significantly down-regulated in primary human breast cancer samples and that the combined expression patterns of KLF17 and Id-1 can serve as a potential biomarker for lymph node metastasis in breast cancer. Overall design: Illumina mouse array was used for 168FARN cells stably expressing a control vector, KLF17 cDNA or KLF17 shRNA. Triplicate samples were used to perform gene expression analysis on each cell line.

INSTRUMENT(S): mouse-6 v1.1 (Illumina)

SUBMITTER: Louise C Showe  

PROVIDER: GSE17081 | GEO | 2009-11-30

SECONDARY ACCESSION(S): PRJNA119801

REPOSITORIES: GEO

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Publications

KLF17 is a negative regulator of epithelial-mesenchymal transition and metastasis in breast cancer.

Gumireddy Kiranmai K   Li Anping A   Gimotty Phyllis A PA   Klein-Szanto Andres J AJ   Showe Louise C LC   Katsaros Dionyssios D   Coukos George G   Zhang Lin L   Huang Qihong Q  

Nature cell biology 20091004 11


Metastasis is a complex multistep process, which requires the concerted action of many genes and is the primary cause of cancer death. Both pathways that regulate metastasis enhancement and those that regulate its suppression contribute to the tumour dissemination process. To identify new metastasis suppressors, we set up a forward genetic screen in a mouse model. We transduced a genome-wide RNA interference (RNAi) library into the non-metastatic 168FARN breast cancer cell line and orthotopicall  ...[more]

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