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Articles 1 - 7 of 7
Full-Text Articles in Life Sciences
Regulation Of E2f1 In Keratinocytes During Uv-Damage And Differentiation, Randeep K. Singh
Regulation Of E2f1 In Keratinocytes During Uv-Damage And Differentiation, Randeep K. Singh
Electronic Thesis and Dissertation Repository
The E2F1 transcription factor regulates the expression of key genes involved in cell proliferation and differentiation to maintain skin homeostasis. The expression of E2F1 is tightly regulated during cell cycle progression and when cells are committed to differentiate, as well as in response to DNA damage. In keratinocytes, E2F1 protein and transcript levels increase following UV-induced DNA damage, whereas, in response to Ca2+-induced differentiation, both E2F1 protein and transcript levels decrease. In this thesis, I examined in detail the mechanism that modulates E2F1 stability following DNA damage and during keratinocyte differentiation. I show that E2F1 associates with hHR23 and together …
Characterization Of The Catalytic Ck2 Subunits With Substitutions At Residues Involved In Inhibitor Binding, Paul Desormeaux
Characterization Of The Catalytic Ck2 Subunits With Substitutions At Residues Involved In Inhibitor Binding, Paul Desormeaux
Electronic Thesis and Dissertation Repository
CK2 is a constitutively active, ubiquitously expressed and pleiotropic serine/threonine protein kinase that is implicated in many cellular functions including tumorigenesis. CK2 has two catalytic subunits, CK2a and CK2a’, that carry out its function in the cell. Previous studies have indicated that inhibitor-refractory mutants have been effective in recovering residual CK2 activity, in the presence of inhibitors, when compared to wild type CK2. Based on these observations, inhibitor-refractory mutants were created for both CK2a and CK2a’ and tested with various concentrations with two CK2-specific inhibitors, CX-4945 and inhibitor VIII. The CK2a triple mutant (V66A/I174A/H160D) was tested in inducible U2OS Flp-In …
Inhibition Of Mt1-Mmp Proteolytic Function And Erk1/2 Signalling Influences Breast Cancer Cell Migration And Invasion Through Changes In Mmp-2 And Mmp-9 Expression, Caitlin L. Evered
Inhibition Of Mt1-Mmp Proteolytic Function And Erk1/2 Signalling Influences Breast Cancer Cell Migration And Invasion Through Changes In Mmp-2 And Mmp-9 Expression, Caitlin L. Evered
Electronic Thesis and Dissertation Repository
Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a multifunctional protease that invokes changes extracellularly via cleavages of ECM substrates, and intracellularly through induction of cell signalling cascades, both to influence cell behaviour and motility. The effects of MT1-MMP activation, MMP catalytic activity, and ERK1/2 signalling were examined by chemically or genetically altering each parameter. Regardless of treatment, expression of the two gelatinases, MMP-2 and -9, were always altered in an inverse relationship. This work proposes a pathway through active MT1-MMP initiation of ERK1/2 phosphorylation and subsequent targeting the NF-κB transcription factor, to ultimately influence MMP-9 expression. Modulation of MT1-MMP activation, …
Characterization Of Numb As A Regulator Of Anaplastic Lymphoma Kinase, Ran Wei
Characterization Of Numb As A Regulator Of Anaplastic Lymphoma Kinase, Ran Wei
Electronic Thesis and Dissertation Repository
Cellular events rely on protein-protein interactions that are often mediated by modular domains which recognize particular sequence motifs in binding partners. The NUMB protein is the first described cell fate determinant and multifaceted adaptor that is involved in a wide variety of cellular events. NUMB mainly mediates protein interactions via its modular PTB domain. Here we present a systematic investigation of the NUMB-PTB interactome by employing an integrative strategy combining both protein and peptide arrays. We profiled NUMB-PTB binding specificity and interacting proteins genome-wide. The receptor tyrosine kinases (RTKs) are found highly enriched in the interactome, raising the possibility that …
The Cytoplasmic Domain Of Membrane-Type 1 Matrix Metalloproteinase Is Required For Its Survival-Promoting, But Not Its Migration-Promoting Function In Mcf-7 Breast Cancer Cells, Jacob Jh Pelling
Electronic Thesis and Dissertation Repository
Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a multifunctional protease that degrades proteins during cell migration, and influences cell survival. Both the protein localization and signal transduction capabilities of MT1-MMP depend on its cytoplasmic domain (CD), indicative of a diverse regulatory function. The effects of CD mutations on cell migration and survival were examined by ectopically expressing MT1-MMP variants in MCF-7 cells. CD alteration by substitution or deletion did not abolish the migration-promoting effects of MT1-MMP, but did decrease cell survival and increase apoptosis. Expression of CD-altered MT1-MMP resulted in a protrusive cell morphology in 3D culture that was lost upon …
Oncolytic Virus Therapy For The Treatment Of Metastatic Ovarian Cancer, Jessica Tong
Oncolytic Virus Therapy For The Treatment Of Metastatic Ovarian Cancer, Jessica Tong
Electronic Thesis and Dissertation Repository
The management of patients with epithelial ovarian cancer (EOC) faces two major challenges which standard treatments fail to effectively address: 1) Diffuse metastasis as a consequence of late stage diagnosis and 2) intra-tumoral heterogeneity, which fuels tumor evolution and drives the acquisition of chemotherapeutic resistance. In this thesis, we tested new therapeutic strategies using a 3-dimensional in vitro spheroid culture model that mimics key steps of epithelial ovarian cancer metastasis; and another model that mimics both temporal and cellular heterogeneity by establishing multiple cell lines from a single patient over the course of disease progression. Using these models, we investigated …
Exploring The Regulation And Function Of Epithelial-Mesenchymal Plasticity In Ovarian Cancer Spheroids, Samah Rafehi
Exploring The Regulation And Function Of Epithelial-Mesenchymal Plasticity In Ovarian Cancer Spheroids, Samah Rafehi
Electronic Thesis and Dissertation Repository
Epithelial-mesenchymal transition (EMT) serves as a key mechanism driving tumour cell migration, invasion, and metastasis in many carcinomas. Transforming growth factor-beta (TGFβ) signalling is implicated in several steps during cancer pathogenesis and acts as a classical inducer of EMT. Since epithelial ovarian cancer (EOC) cells have the potential to switch between epithelial and mesenchymal states during metastasis, we predicted that modulation of TGFβ signalling would significantly impact EMT and the malignant potential of EOC spheroid cells. Ovarian cancer patient ascites-derived cells naturally underwent an EMT response when aggregating into spheroids, and this was reversed upon spheroid re-attachment to a …