When combined with previous studies, our data suggest that dual induction of PAR-2-NFκB inflammatory signaling and PI3K-Akt-mTor survival/proliferative signaling underlies the transforming potential of matriptase and may contribute to pro-tumorigenic signaling in human epithelial carcinogenesis.
We then determined whether fisetin and 5-FU together or singly affected tumorigenesis in Apc<sup>Min/+</sup> mice that also express constitutively active PI3K in the distal small intestine and colon.
We observed a significant increase in a genomic signature of phosphatidylinositol 3-kinase (PI3K) pathway activation in the cytologically normal bronchial airway of smokers with lung cancer and smokers with dysplastic lesions, suggesting that PI3K is activated in the proximal airway before tumorigenesis.
We hypothesized that aberrant methylation and hence altered expression of certain unknown important genes induced by the genetically activated PI3K pathway signaling is a major epigenetic mechanism in human tumorigenesis.
We highlight the importance of PTEN loss leading to activation of the oncogenic PI3K/Akt/mTOR pathway in tumorigenesis and progression, which can be attributed to both genetic and non-genetic alterations involving gene mutation, loss of heterozygosity, promoter hypermethylation, and microRNA mediated negative regulation.
We have for the first time revealed that MT1G appears to be functional tumor suppressor involved in thyroid carcinogenesis mainly through modulating the phosphatidylinositol-3-kinase (PI3K)/Akt pathway and partially through regulating the activity of Rb/E2F pathway in this study.
We further show that superactivation of the prosurvival PI3K-AKT signaling pathway limits the efficacy of a PARP single-agent treatment, and that PARP and PI3K inhibitors effectively synergize to suppress tumorigenesis in human prostate cancer cell lines and in a Pten/Trp53-deficient mouse model of advanced prostate cancer.
We concluded that 3,6-DHF upregulates miR-34a via inhibiting DNMT1 and hypermethylation, whereas downregulates miR-21 by modulating histone modification, and consequently suppresses the PI3K/Akt/mTOR signaling pathway in breast carcinogenesis.
We also discussed how targeting the Akt and MEK, downstream effectors of the PI3K/Akt and MAPK pathways, respectively, would probably pave the possible molecular therapeutic target for the ras driven tumorigenesis in oral cancer.
We also discuss the implications of targeting Akt and/or mTOR, which are the downstream effectors of PI3K that may possibly pave the way for molecular therapeutic targets for PIK3CA-driven oral carcinogenesis.
Vav3 is a multiple function protein with both signaling molecule and coactivator activities. sPLA2-IIa is a downstream effector of HER/HER2-PI3K-Akt-NF-κB signaling and involved in inflammatory response and tumorigenesis.
Using dominant negative GAB1 mutants lacking canonical tyrosine residues for SHP2 and PI3K interactions or lentiviral shRNA that targets GAB1, we demonstrate that GAB1 phosphorylation is required for ERBB2 mutant-induced cell signaling, cell transformation, and tumorigenesis.
Tumor silencing of NOS and LOX signaling mirrored the antitumor effect of the hit compounds, demonstrating their participation in Notch-PI3K/Akt-induced tumorigenesis.
TSSC3 promotes autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway to suppress tumorigenesis and metastasis in osteosarcoma, and predicts a favorable prognosis.
Transcriptome analysis revealed that major transcription factors, such as SRF, HNF4A, ZEB1, and RUNX1, with potential regulatory roles in key pathways, including focal adhesion, the PI3K-Akt signaling pathway, and the MAPK signaling pathway, may play a role in the tumorigenesis of SRCC.
Together, these data suggested that CCR9-CCL25 interaction induced tumorigenesis of NSCLC cells and that this induction might be accomplished through the activation of the PI3K/Akt pathway.
Together, our findings suggest that HBc promotes tumorigenesis of hepatoma cells by enhancing the expression of total Src and the active form of the kinase and subsequently activates Src/PI3K/Akt signaling pathway, revealing novel insights into the underlying mechanisms of HBV-associated hepatocarcinogenesis.-Liu, W., Guo, T.-F., Jing, Z.-T., Yang, Z., Liu, L., Yang, Y.-P., Lin, X., Tong, Q.-Y.
Together with the in vivo data demonstrating a strong tumor-promoting activity of PRR14 and the mutants, our work uncovered this proline-rich protein as a novel activator of the PI3K pathway that promoted tumorigenesis in lung cancer.
To investigate if analysis of genetic alterations in the main pathways involved in endometrioid type carcinogenesis (PI3K-AKT, Wnt/β-catenin, P53-activation and MSI) improves the current risk assessment based on clinicopathological factors.
To identify pathways that support PI3Koncogenesis, we performed a genome-wide RNAi screen in isogenic cell lines harboring wild-type or mutant PIK3CA to search for PI3K synthetic-lethal (SL) genes.
To directly test how the PI3K and Ras/MAPK pathways contribute to tumorigenesis, we deleted PTEN and activated KRas within non-tumorigenic MCF-10A breast cells.