Angiogenic and metastatic genes changed in RKO cells (colorectal cancer) upon perturbation of key components of AKT pathway.
| PAG Title | Angiogenic and metastatic genes changed in RKO cells (colorectal cancer) upon perturbation of key components of AKT pathway. |
| PAG ID | MAX000033 |
| Type | A |
| Source Link |  MSigDB |
| Publication Reference | NA |
| PAG Description | Our laboratory has delineated that the phosphatidylinositol 3' kinase (PI3K)/AKT/I kappa B kinase (IKK) pathway positively regulates NF kappa B and beta-catenin, both important transcriptional regulators in colorectal cancer (CRC). Therefore, we investigated the effect of inhibiting the PI3K/AKT/IKK alpha pathway in regulating the inappropriate constitutive activation of NF kappa B and beta-catenin in CRC cell lines. SW480 and RKO CRC cell lines demonstrate constitutive activation of AKT as well as both NF kappa B- and beta-catenin-dependent transcription. The constitutive activation of NF kappa B- and beta-catenin-dependent transcription is inhibited by transiently transfecting either kinase dead (KD) IKK alpha, which blocks IKK alpha kinase activity, KD AKT, which blocks AKT activity, or wildtype (WT) PTEN, which inhibits PI3K and AKT activity. The ability of KD IKK alpha, KD AKT or WT PTEN to decrease beta-catenin-dependent transcription is independent of their effects on NF kappa B. Inducible expression of either KD IKK alpha or WT PTEN strongly inhibits both the constitutive NF kappa B- and beta-catenin-dependent promoter and endogenous gene activation. Targeted array-based gene expression analysis of this inducible system reveals that many of the genes downregulated upon inhibition of this pathway are involved in tumor angiogenesis and metastasis. The activation of this pathway and the expression of the three most repressed genes was further analysed in samples of CRC. These results indicate a role of this pathway in controlling gene expression important in tumor progression and metastasis. |
| Species | Homo sapiens |
| nCoCo Score | 934 |
| Base PAG ID | MAX000033 |
| Human Phenotyte Annotation | |
| Curator | PAGER curation team |
| Curator Contact | PAGER-contact@googlegroups.com |
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