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One or more keywords matched the following properties of Howe, Philip
overview Research in the Howe laboratory is focused on understanding the signaling pathways activated by transforming growth factor ß1 (TGFß1), interleukin-like EMT inducer (ILEI) and Wnt in cellular models of differentiation and cancer. One major area of interest is a recently identified signaling pathway whereby TGFß regulates epithelial-mesenchymal transitions (EMT) and metastasis through a post-transcriptional mechanism involving the regulation of an RNA binding protein, heterogeneous ribonucleoprotein E1 (hnRNP E1). We are focused on how TGFß regulation of hnRNP E1 phosphorylation not only regulates translational silencing of select mRNAs involved in EMT/metastasis but also of lncRNAs that may also contribute to tumor progression. Candidate mRNA targets and lncRNAs are actively being pursued and one mRNA target in particular, the cytokine ILEI, has become a major focus of the laboratory. Aside from its known role in EMT, relatively little is known regarding ILEI. We have identified ILEI as a potent stem factor in breast epithelium and are actively investigating the molecular mechanisms through which it mediates its progenitor effects. In another focus area we are investigating the role of the adaptor molecule, disabled-2 (Dab2), as a mediator of the cross-talk between the TGFß and Wnt signaling pathways. We have shown that the tumor suppressor functions of Dab2 are mediated thru its attenuation of canonical Wnt/ß-catenin signaling by selectively recruiting the Wnt co-receptor LRP6 to the clathrin-dependent endocytic route, thereby sequestering it from caveolin-mediated endocytosis and signaling. TGFß levels in cells and tissues regulates Dab2 expression and thereby regulates, thru Dab2, Wnt signaling. We are currently investigating this cross-talk in the developing zebrafish and in animal tumor models. We have also made the recent observation that Dab2 regulates TGFß-induced apoptosis and autophagy. We have shown that mechanistically Dab2 serves as a molecular switch to control whether cells undergo apoptosis or autophagy in response to TGFß, and significantly this switch may be underlie chemosensitivity and acquired-resistance during tumorigenesis.
One or more keywords matched the following items that are connected to Howe, Philip
Item TypeName
Academic Article Regulation of clusterin gene expression by transforming growth factor beta.
Academic Article Caspase inhibitor BD-fmk distinguishes transforming growth factor beta-induced apoptosis from growth inhibition.
Academic Article Mechanisms of TGF-beta-induced cell cycle arrest.
Academic Article Transforming growth factor beta regulates clusterin gene expression via modulation of transcription factor c-Fos.
Academic Article Loss of transforming growth factor beta 1 (TGF-beta 1)-induced growth arrest and p34cdc2 regulation in ras-transfected epithelial cells.
Academic Article TGF-beta induces fibronectin synthesis through a c-Jun N-terminal kinase-dependent, Smad4-independent pathway.
Academic Article Transforming growth factor beta induces caspase 3-independent cleavage of alphaII-spectrin (alpha-fodrin) coincident with apoptosis.
Academic Article Smad3 potentiates transforming growth factor beta (TGFbeta )-induced apoptosis and expression of the BH3-only protein Bim in WEHI 231 B lymphocytes.
Academic Article Secreted transforming growth factor beta2 activates NF-kappaB, blocks apoptosis, and is essential for the survival of some tumor cells.
Academic Article Analysis of TGF-beta-mediated synthesis of extracellular matrix components.
Academic Article Promoter analysis of TGF-beta responsive genes by transient transfection and deletional/mutational analysis.
Academic Article Regulation of AP-1 activity by TGF-beta.
Academic Article Analysis of TGF-beta-inducible apoptosis.
Academic Article Transforming growth factor beta 1 inhibition of p34cdc2 phosphorylation and histone H1 kinase activity is associated with G1/S-phase growth arrest.
Academic Article Smad7 is induced by CD40 and protects WEHI 231 B-lymphocytes from transforming growth factor-beta -induced growth inhibition and apoptosis.
Academic Article Distinct pathways regulate transforming growth factor beta 1-stimulated proto-oncogene and extracellular matrix gene expression.
Academic Article Inhibition of mink lung epithelial cell proliferation by transforming growth factor-beta is coupled through a pertussis-toxin-sensitive substrate.
Academic Article HOXA9 participates in the transcriptional activation of E-selectin in endothelial cells.
Academic Article TGF-beta-mediated phosphorylation of hnRNP E1 induces EMT via transcript-selective translational induction of Dab2 and ILEI.
Academic Article Transforming growth factor beta 1 treatment of AKR-2B cells is coupled through a pertussis-toxin-sensitive G-protein(s).
Academic Article Identification of an mRNP complex regulating tumorigenesis at the translational elongation step.
Academic Article 3'-UTR-mediated post-transcriptional regulation of cancer metastasis: beginning at the end.
Academic Article Myosin II isoform switching mediates invasiveness after TGF-?-induced epithelial-mesenchymal transition.
Academic Article Interferon alpha/beta modulation of growth-factor-stimulated mitogenicity in AKR-2B fibroblasts.
Academic Article Establishment of a TGF?-induced post-transcriptional EMT gene signature.
Academic Article The oncoprotein Ski acts as an antagonist of transforming growth factor-beta signaling by suppressing Smad2 phosphorylation.
Academic Article The regulation of cell proliferation by serum growth factors.
Academic Article Transforming growth factor beta 1-mediated inhibition of smooth muscle cell proliferation is associated with a late G1 cell cycle arrest.
Academic Article Release from G1 growth arrest by transforming growth factor beta 1 requires cellular ras activity.
Academic Article Interaction of transforming growth factor beta receptors with apolipoprotein J/clusterin.
Academic Article Transforming growth factor beta (TGF beta)-induced nuclear localization of apolipoprotein J/clusterin in epithelial cells.
Academic Article Inactivation of p27Kip1 by the viral E1A oncoprotein in TGFbeta-treated cells.
Academic Article The retinoid antagonist MX781 induces clusterin expression in prostate cancer cells via heat shock factor-1 and activator protein-1 transcription factors.
Academic Article Disabled-2 (Dab2) is required for transforming growth factor beta-induced epithelial to mesenchymal transition (EMT).
Academic Article Disabled-2 (Dab2) mediates transforming growth factor beta (TGFbeta)-stimulated fibronectin synthesis through TGFbeta-activated kinase 1 and activation of the JNK pathway.
Academic Article Tumor necrosis factor alpha (TNF-alpha) receptor-II is required for TNF-alpha-induced leukocyte-endothelial interaction in vivo.
Academic Article The inhibitory effects of Disabled-2 (Dab2) on Wnt signaling are mediated through Axin.
Academic Article TGF beta-mediated BIM expression and apoptosis are regulated through SMAD3-dependent expression of the MAPK phosphatase MKP2.
Academic Article Transforming growth factor beta (TGFbeta)-induced apoptosis: the rise & fall of Bim.
Academic Article Runx1 is a co-activator with FOXO3 to mediate transforming growth factor beta (TGFbeta)-induced Bim transcription in hepatic cells.
Academic Article The tale of transforming growth factor-beta (TGFbeta) signaling: a soign? enigma.
Academic Article Central role for disabled-2 in mesenchymal stem cardiac protein expression and functional consequences after engraftment in acute myocardial infarction.
Academic Article Type II transforming growth factor-beta receptor recycling is dependent upon the clathrin adaptor protein Dab2.
Academic Article Regulation of transforming growth factor beta 1 action by multiple transducing pathways: evidence for both G protein-dependent and -independent signaling.
Academic Article Inhibition of G1 phase cyclin dependent kinases by transforming growth factor beta 1.
Academic Article Inhibition of interferon-gamma-induced major histocompatibility complex class II gene transcription by interferon-beta and type beta 1 transforming growth factor in human astrocytoma cells. Definition of cis-element.
Academic Article Oxidized low density lipoprotein and lysophosphatidylcholine stimulate cell cycle entry in vascular smooth muscle cells. Evidence for release of fibroblast growth factor-2.
Academic Article Isolation and characterization of mutant cell lines defective in transforming growth factor beta signaling.
Academic Article TGF-beta suppresses IFN-gamma induction of class II MHC gene expression by inhibiting class II transactivator messenger RNA expression.
Concept Transforming Growth Factor beta
Concept Leukemia Inhibitory Factor Receptor alpha Subunit
Concept Receptors, Transforming Growth Factor beta
Concept Peptide Elongation Factor 1
Concept Platelet-Derived Growth Factor
Concept Microphthalmia-Associated Transcription Factor
Concept Transforming Growth Factor beta2
Concept STAT3 Transcription Factor
Concept Eukaryotic Initiation Factor-1
Concept GATA4 Transcription Factor
Concept Receptors, Tumor Necrosis Factor, Type II
Concept Tumor Necrosis Factor-alpha
Concept Transforming Growth Factor beta1
Concept Transcription Factor AP-1
Concept Core Binding Factor Alpha 2 Subunit
Concept Epidermal Growth Factor
Concept Fibroblast Growth Factor 2
Academic Article Neuropilin-2 Is upregulated in lung cancer cells during TGF-?1-induced epithelial-mesenchymal transition.
Academic Article Cathepsin-B-mediated cleavage of Disabled-2 regulates TGF-?-induced autophagy.
Academic Article The La protein counteracts cisplatin-induced cell death by stimulating protein synthesis of anti-apoptotic factor Bcl2.
Academic Article Identification and characterization of an hnRNP E1 translational silencing motif.
Academic Article Transforming Growth Factor-? Is an Upstream Regulator of Mammalian Target of Rapamycin Complex 2-Dependent Bladder Cancer Cell Migration and Invasion.
Academic Article Translational regulation of inhibin ?A by TGF? via the RNA-binding protein hnRNP E1 enhances the invasiveness of epithelial-to-mesenchymal transitioned cells.
Academic Article Surface Expression of TGF? Docking Receptor GARP Promotes Oncogenesis and Immune Tolerance in Breast Cancer.
Academic Article Membrane-organizing protein moesin controls Treg differentiation and antitumor immunity via TGF-? signaling.
Academic Article TGF-beta signaling in cancer: post-transcriptional regulation of EMT via hnRNP E1.
Academic Article Interleukin-like EMT inducer regulates partial phenotype switching in MITF-low melanoma cell lines.
Academic Article The Long (lncRNA) and Short (miRNA) of It: TGF?-Mediated Control of RNA-Binding Proteins and Noncoding RNAs.
Academic Article TGF-? receptor I/II trafficking and signaling at primary cilia are inhibited by ceramide to attenuate cell migration and tumor metastasis.
Academic Article Interleukin-like EMT inducer (ILEI) promotes melanoma invasiveness and is transcriptionally up-regulated by upstream stimulatory factor-1 (USF-1).
Academic Article TGF? promotes breast cancer stem cell self-renewal through an ILEI/LIFR signaling axis.
Academic Article TGF?-induced expression of long noncoding lincRNA Platr18 controls breast cancer axonogenesis.
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