New Wnt/β-catenin target genes promote experimental metastasis and migration of colorectal cancer cells through different signals
作者： Yong Yu , Özlem Akilli Öztürk , Jane D Holland , Daniel Besser , Johannes Fritzmann
DOI: 10.1136/GUTJNL-2014-307900
关键词:
摘要: Objectives We have previously identified a 115-gene signature that characterises the metastatic potential of human primary colon cancers. The included canonical Wnt target gene BAMBI , which promoted experimental metastasis in mice. Here, we three new direct genes from signature, and studied their functions epithelial–mesenchymal transition (EMT), cell migration metastasis. Design examined liver metastases following injection selected tumour cells into spleens NOD/SCID Molecular cellular techniques were used to identify transcription Wnt/β-catenin signals. Microarray analyses experiments interfered with through inhibitors performed characterise downstream signalling systems. Results Three colorectal cancer (CRC) BOP1 CKS2 NFIL3 as targets β-catenin/TCF4. Overexpression knocking down these CRC inhibited, respectively, mice, EMT motility culture. Cell was repressed by interfering distinct systems PI3K, JNK, p38 mitogen-activated protein kinase and/or mTOR. Gene expression profiling series migration-promoting genes, induced BOP1, NFIL3, could be are specific pathways. Conclusions EMT, cells. These crosstalk different systems, activate genes. pathways may serve therapeutic treatment
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