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Articles 1 - 12 of 12

Full-Text Articles in Cancer Biology

Regulation Of Canonical And Non-Canonical Hippo Pathway Components In Mitosis And Cancer, Seth Stauffer Dec 2018

Regulation Of Canonical And Non-Canonical Hippo Pathway Components In Mitosis And Cancer, Seth Stauffer

Theses & Dissertations

The Hippo pathway is conserved regulator of organ size through control of proliferation, apoptosis, and stem-cell self-renewal. In addition to this important function, many of the canonical signaling members have also been shown to be regulated during mitosis. Importantly, Hippo pathway components are frequently dysregulated in cancers and have attracted attention as possible targets for improved cancer therapeutics. Further exploration of Hippo-YAP (yes-associated protein) signaling has revealed new regulators and effectors outside the canonical signaling network and has revealed a larger non-canonical network of signaling proteins in which canonical Hippo pathway components crosstalk with important cellular homeostasis and apoptosis signaling ...


The Role Of Yes-Associated Protein 1 In Ovarian Physiology And Pathology, Xiangmin Lv Dec 2017

The Role Of Yes-Associated Protein 1 In Ovarian Physiology And Pathology, Xiangmin Lv

Theses & Dissertations

Ovarian granulosa cells are the major somatic components of the ovarian follicle. Proper proliferation and differentiation of ovarian granulosa cells are essential for successful follicle development. Accumulating evidence indicates that the Hippo-YAP signaling pathway plays critical roles in both development and tumorigenesis of several organs. The present study aims to investigate the role of Yes-associated protein 1 (YAP) in ovarian granulosa cell proliferation, differentiation, and malignant transformation. At first, we found that nuclear YAP (active) was highly expressed in proliferative granulosa cells, whereas cytoplasmic YAP (inactive) was detected mainly in terminally-differentiated luteal cells. Further studies suggested that endogenous YAP activity ...


Identifying The Role Of Janus Kinase 1 In Mammary Gland Development And Breast Cancer, Barbara Swenson Dec 2017

Identifying The Role Of Janus Kinase 1 In Mammary Gland Development And Breast Cancer, Barbara Swenson

Theses & Dissertations

The development of the postnatal mammary gland is tightly controlled by peptide hormones and cytokines. The signaling of these extracellular ligands through their corresponding receptors rely on Janus Kinases (JAKs) that activate downstream Signal Transducers and Activators of Transcription (STATs). The JAK/STAT signaling pathway is crucial for processes such as growth, proliferation, and cell survival of the epithelial tissue, but also for the breakdown and remodeling of the mammary gland via IL-6 class inflammatory cytokines (e.g. LIF and OSM). JAK1 and JAK2, which are expressed in the mammary gland, are thought to have redundant functions. However, our previous ...


The Role Of Ehd2 In Triple-Negative Breast Cancer Tumorigenesis And Progression, Timothy A. Bielecki May 2017

The Role Of Ehd2 In Triple-Negative Breast Cancer Tumorigenesis And Progression, Timothy A. Bielecki

Theses & Dissertations

Triple-negative breast cancer (TNBC) comprises 10%-15% of all breast cancer cases, yet is clinically challenging due to lack of targeted therapies which leads to higher mortality. Molecular subtyping has identified the most aggressive subclasses of breast cancer to be enriched in components of caveolae. While caveolae have been linked to many biological processes, their precise role in TNBC is still poorly understood. EHD2, a member of the C-terminal EPS15-Homology Domain-containing (EHD) protein family, has emerged as a new regulator of caveolae dynamics and is essential to maintain a stable membrane pool of caveolae. Studies in model cells demonstrate that ...


Regulation Of Alteration/Deficiency In Activation 3 (Ada3) By Acetylation And Its Role In Cell Cycle Regulation And Oncogenesis, Shashank Srivastava Dec 2016

Regulation Of Alteration/Deficiency In Activation 3 (Ada3) By Acetylation And Its Role In Cell Cycle Regulation And Oncogenesis, Shashank Srivastava

Theses & Dissertations

The ADA3 (Alteration/Deficiency in Activation 3) protein is a transcriptional adaptor protein that was initially discovered as a component of several HAT (Histone Acetyltransferase) complexes, the enzyme complex responsible for histone acetylation, which is a prerequisite for transcription. Earlier the studies from Dr. Band’s laboratory and that of others’ have deciphered a crucial role of ADA3 in cell cycle regulation (both through G1/S and G2/M phase transitions) and in maintaining the genomic stability.

While our laboratory investigated the mechanism behind the role of ADA3 in G1/S transition, the same remained unknown for ...


Role Of Ddr1 In Pancreatic Cancer, Huocong Huang Aug 2016

Role Of Ddr1 In Pancreatic Cancer, Huocong Huang

Theses & Dissertations

Pancreatic ductal adenocarcinomas are highly malignant cancers, characterized by extensive invasion into surrounding tissues, metastasis to distant organs at a very early stage, and a limited response to therapy. One of the main features of pancreatic ductal adenocarcinomas is desmoplasia, which leads to extensive deposition of collagen I. We have demonstrated that collagen I can induce epithelial-mesenchymal transition (EMT) in pancreatic cancer cells. A hallmark of EMT is an increase in the expression of a mesenchymal cadherin, N-cadherin. Our previous studies have shown that up-regulation of N-cadherin can promote tumor cell invasion and that collagen I-induced EMT is through two ...


Sprouty 2: A Novel Attenuator Of B Cell Receptor And Mapk Signaling In Chronic Lymphocytic Leukemia, Ashima Shukla May 2016

Sprouty 2: A Novel Attenuator Of B Cell Receptor And Mapk Signaling In Chronic Lymphocytic Leukemia, Ashima Shukla

Theses & Dissertations

Clinical heterogeneity is a major barrier to effective treatment of Chronic Lymphocytic Leukemia (CLL). Emerging evidence suggests that constitutive activation of various signaling pathways plays a role in the heterogeneous clinical outcome of CLL patients. MAPK-Erk signaling represents one such pathway with a demonstrated role in CLL pathogenesis. In this study, we have investigated the role of Sprouty2 (SPRY2) as a negative regulator of receptor and non-receptor tyrosine kinase signaling in the pathogenesis of CLL. We show that SPRY2 expression is significantly decreased in CLL cells, particularly from poor prognosis patients compared to those from good prognosis patients. Over-expression of ...


Role Of Cell Type And Genetic Alterations In Driving Breast Cancer Pathogenesis, Divya Bhagirath May 2016

Role Of Cell Type And Genetic Alterations In Driving Breast Cancer Pathogenesis, Divya Bhagirath

Theses & Dissertations

Breast cancer is the second most leading cause of death among women in the United States. Several environmental and genetic factors contribute to the pathogenesis of the disease. It is classified into different subtypes based on expression of certain markers as well as that of set of genes that define the disease progression and associated mortality. Identification of various subtypes namely: Luminal-like (Luminal-A, Luminal-B), ErbB2 over-expressing, Basal-like and Claudin low types, showed an association of survival outcomes with that of the corresponding gene expression signatures, thus paving a way for therapeutic intervention. It further emphasizes the importance of nature of ...


Defining The Role Of Interferon Regulatory Factor 4 In Chronic Lymphocytic Leukemia., Vipul Shukla May 2016

Defining The Role Of Interferon Regulatory Factor 4 In Chronic Lymphocytic Leukemia., Vipul Shukla

Theses & Dissertations

Chronic Lymphocytic Leukemia (CLL) represents the most common adult leukemia in the Western hemisphere. Despite considerable progress in our current understanding of CLL, this disease remains incurable and the molecular events underlying the complex pathogenesis of CLL are not fully elucidated. Interferon Regulatory Factor 4 (IRF4) belongs to the IRF superfamily of transcription factors that has been shown to play critical roles at multiple stages of B cell development. Interestingly, a Genome Wide Association Study identified Single Nucleotide Polymorphism (SNP) mediated IRF4 down regulation, as a major predisposing genetic event during the development of CLL. However, whether low levels of ...


The Role Of Tumor Suppressor Co-Chaperone Chip/Stub1 In Erbb2-Mediated Oncogenesis, Haitao Luan Dec 2015

The Role Of Tumor Suppressor Co-Chaperone Chip/Stub1 In Erbb2-Mediated Oncogenesis, Haitao Luan

Theses & Dissertations

The epidermal growth factor receptor (EGFR) family member ErbB2 (Her2) is overexpressed in 20 -30% of invasive breast cancers and this overexpression correlates with poor prognosis and shorter overall as well as disease-free survival. Aberrant expression of ErbB2 through gene amplification, transcriptional deregulation and/or altered endocytic trafficking results in overexpression of ErbB2 at the plasma membrane and biases ErbB2 from primarily ligand-driven hetero-dimerization under normal expression conditions to increased ligand-independent homo-dimer and hetero-dimer formation and consequent activation. C-terminus of HSC70-Inteeracting protein (CHIP)/STIP1-homologous U-Box containing protein 1 (STUB1) is an HSP90/HSC70 interacting negative co-chaperone known to promote ubiquitination ...


Role Of Hippo-Yap Signaling In Mitosis And Prostate Cancer, Lin Zhang Aug 2015

Role Of Hippo-Yap Signaling In Mitosis And Prostate Cancer, Lin Zhang

Theses & Dissertations

The Hippo pathway controls organ size and tumorigenesis by inhibiting cell proliferation and promoting apoptosis. KIBRA [kidney and brain expressed protein] is an upstream regulator of the Hippo-YAP signaling. The role KIBRA plays in mitosis has not been established. We show that KIBRA activates the Aurora kinases during mitosis and KIBRA promotes the phosphorylation of large tumor suppressor 2 by activating Aurora-A. We further show that knockdown of KIBRA causes mitotic abnormalities, including defects of spindle and centrosome formation and chromosome misalignment. The transcriptional co-activator with PDZ-binding motif is a downstream effector of the Hippo tumor suppressor pathway. In the ...


Lgr5 Activates Tgfβ Signaling And Suppresses Metastasis In Colon Cancer, Xiaolin Zhou May 2015

Lgr5 Activates Tgfβ Signaling And Suppresses Metastasis In Colon Cancer, Xiaolin Zhou

Theses & Dissertations

Metastasis is the major cause of death in colorectal cancer patients, mainly due to the ineffectiveness of current therapies once metastases begin to form. Further insight into the biology of colorectal cancer metastasis is, therefore, essential in order to gain a greater understanding of this process and ultimately to develop better cancer therapies to prevent or target metastasis. LGR5 is leucine-rich repeat containing G protein-coupled receptor (GPCR) and was discovered as a marker for proliferating adult stem cells in the small intestine. LGR5 and its homologs LGR4 and LGR6 are receptors of R-spondins (RSPOs), which are secreted agonists of canonical ...