Plasminogen activator inhibitor (PAI-)1 is associated with cancer progression, fibrosis and thrombosis. It is expressed in the stomach but the mechanisms controlling its expression there, and its biological role, are uncertain. We sought to define the role of gastrin in regulating PAI-1 expression and to determine the relevance for gastrin-stimulated cell migration and invasion. In gastric biop...

Regulation of endothelial cell biology by the Notch signaling pathway (Notch) is essential to vascular development, homeostasis, and sprouting angiogenesis. While Notch determines cellfate and differentiation in a wide variety of cells, the molecular basis of upstream regulation of Notch remains poorly understood. Our group and others have implicated the Krüppel-like factor family of transcript...

The presence of somatic B-catenin mutations in some prostate cancers implies that aberrant WNT signaling is involved in the cancer development. Although B-catenin stability is regulated by a multicomponent destruction complex, mutational alterations of B-catenin or other components of the destruction complexes are rare in prostate tumors. Therefore, B-catenin may be regulated by another protein...

Epidemiological studies implicate dietary soy isoflavones as breast cancer preventives, especially due to their anti-estrogenic properties. However, soy isoflavones may also have a role in promoting breast cancer, which has yet to be clarified. We previously reported that equol, a metabolite of the soy isoflavone daidzein, may advance breast cancer potential via upregulation of the eukaryotic i...

We have further defined mechanism(s) by which OSU-03012 (OSU), a derivative of the COX2 inhibitor Celecoxib but lacking COX2 inhibitory activity, kills transformed cells. In cells lacking expression of PKR-like endoplasmic reticulum kinase (PERK -/-) the lethality of OSU was attenuated. OSU enhanced the expression of Beclin 1 and ATG5 and cleavage of pro-caspase 4 in a PERK-dependent fashion an...

During tumor progression, epithelial ovarian cancer (EOC) cells undergo epithelialto-mesenchymal transition (EMT), which influences metastatic success. Mutationdependent activation of Wnt/β-catenin signaling has been implicated in gain of mesenchymal phenotype and loss of differentiation in several solid tumors; however, similar mutations are rare in most EOC histotypes. Nevertheless, evidence ...

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily and has selective antitumor activity. Although TNF-α-induced intracellular signaling pathways have been well studied, TRAIL signaling is not fully understood. Here, we identified a novel TRAIL receptor-binding protein, protein arginine methyltransferase 5 (PRMT5), as a result of proteomic sc...

Inhibitor of DNA binding 1 (Id-1) has been implicated in tumor angiogenesis by regulating the expression of vascular endothelial growth factor (VEGF), but its molecularmechanismhasnotbeen fully understood.Here, weshow the cross talk between Id-1 and hypoxia-inducible factor-1A (HIF-1A), that Id-1 induces VEGF by enhancing the stability and activity of HIF-1A in human endothelial and breast canc...

In most species, oocytes lack centrosomes. Accurate meiotic spindle assembly and chromosome segregation -essential to prevent miscarriage or developmental defectsthus occur through atypical mechanisms that are not well characterized. Using quantitative in vitro and in vivo functional assays in the C. elegans oocyte, we provide here novel evidence that the kinesin-13 KLP-7 promotes the destabili...

26 Interferon (IFN)-β is a major component of innate immunity in mammals, but information on 27 the in vivo source of this cytokine after pathogen infection is still scarce. To identify the cell 28 types responsible for IFN-β production during viral encephalitis, we used reporter mice that 29 express firefly luciferase under control of the IFN-β promoter and stained organ sections with 30 lucif...