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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 TGF-beta induces fibronectin synthesis through a c-Jun N-terminal kinase-dependent, Smad4-independent pathway.
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 Role of CL-100, a dual specificity phosphatase, in thrombin-induced endothelial cell activation.
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 TGF-beta-mediated phosphorylation of hnRNP E1 induces EMT via transcript-selective translational induction of Dab2 and ILEI.
Academic Article 3'-UTR-mediated post-transcriptional regulation of cancer metastasis: beginning at the end.
Academic Article Establishment of a TGF?-induced post-transcriptional EMT gene signature.
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 Transforming growth factor beta (TGF beta)-induced nuclear localization of apolipoprotein J/clusterin in epithelial cells.
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 Runx1 is a co-activator with FOXO3 to mediate transforming growth factor beta (TGFbeta)-induced Bim transcription in hepatic cells.
Academic Article Heterogeneous nuclear ribonucleoproteins (hnRNPs) in cellular processes: Focus on hnRNP E1's multifunctional regulatory roles.
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 TGF-beta suppresses IFN-gamma induction of class II MHC gene expression by inhibiting class II transactivator messenger RNA expression.
Concept RNA
Concept RNA, Small Interfering
Concept RNA, Heterogeneous Nuclear
Concept RNA Precursors
Concept RNA Interference
Concept RNA, Bacterial
Concept RNA Splice Sites
Concept RNA, Messenger
Concept RNA, Transfer
Concept RNA Processing, Post-Transcriptional
Concept RNA Polymerase II
Concept RNA-Binding Proteins
Academic Article Cathepsin-B-mediated cleavage of Disabled-2 regulates TGF-?-induced autophagy.
Academic Article PCBP1/HNRNP E1 Protects Chromosomal Integrity by Translational Regulation of CDC27.
Academic Article Identification and characterization of an hnRNP E1 translational silencing motif.
Academic Article Computational Identification of Post Translational Modification Regulated RNA Binding Protein Motifs.
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 Repression of caspase-3 and RNA-binding protein HuR cleavage by cyclooxygenase-2 promotes drug resistance in oral squamous cell carcinoma.
Academic Article Fbxo4-mediated degradation of Fxr1 suppresses tumorigenesis in head and neck squamous cell carcinoma.
Academic Article TGF-beta signaling in cancer: post-transcriptional regulation of EMT via hnRNP E1.
Academic Article The Long (lncRNA) and Short (miRNA) of It: TGF?-Mediated Control of RNA-Binding Proteins and Noncoding RNAs.
Academic Article EMT does not work regular shifts.
Academic Article A regulated PNUTS mRNA to lncRNA splice switch mediates EMT and tumour progression.
Academic Article SPOt: A novel and streamlined microarray platform for observing cellular tRNA levels.
Academic Article Metabolic Labeling and Profiling of Transfer RNAs Using Macroarrays.
Academic Article TGF? promotes breast cancer stem cell self-renewal through an ILEI/LIFR signaling axis.
Academic Article RNA binding protein PCBP1 is an intracellular immune checkpoint for shaping T cell responses in cancer immunity.
Concept RNA, Long Noncoding
Academic Article Heterogeneous nuclear ribonucleoprotein E1 binds polycytosine DNA and monitors genome integrity.
Academic Article TGF?-induced expression of long noncoding lincRNA Platr18 controls breast cancer axonogenesis.
Academic Article The ubiquitin E3 ligase ARIH1 regulates hnRNP E1 protein stability, EMT and breast cancer progression.
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