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Cancer Biology Commons

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Articles 1 - 11 of 11

Full-Text Articles in Cancer Biology

The Msi Family Of Rna-Binding Proteins Function Redundantly As Intestinal Oncoproteins, Ning Li, Maryam Yousefi, Angela Nakauka-Ddamba, Fan Li, Lee Vandivier, Kimberly Parada, Dong-Hun Woo, Shan Wang, Ammar S. Naqvi, Shilpa Rao, John Tobias, Ryan J. Cedeno, Gerard Minuesa, Katz Y, Trevor S. Barlowe, Alexander James Valvezan, Sheila Shankar, Raquel R. Deering, Peter S. Klein, Shane T. Jensen, Michael G. Kharas, Brian D. Gregory, Zhengquan Yu, Christopher J. Lengner Dec 2015

The Msi Family Of Rna-Binding Proteins Function Redundantly As Intestinal Oncoproteins, Ning Li, Maryam Yousefi, Angela Nakauka-Ddamba, Fan Li, Lee Vandivier, Kimberly Parada, Dong-Hun Woo, Shan Wang, Ammar S. Naqvi, Shilpa Rao, John Tobias, Ryan J. Cedeno, Gerard Minuesa, Katz Y, Trevor S. Barlowe, Alexander James Valvezan, Sheila Shankar, Raquel R. Deering, Peter S. Klein, Shane T. Jensen, Michael G. Kharas, Brian D. Gregory, Zhengquan Yu, Christopher J. Lengner

Departmental Papers (Biology)

Members of the Msi family of RNA-binding proteins have recently emerged as potent oncoproteins in a range of malignancies. MSI2 is highly expressed in hematopoietic cancers, where it is required for disease maintenance. In contrast to the hematopoietic system, colorectal cancers can express both Msi family members, MSI1 and MSI2. Here, we demonstrate that, in the intestinal epithelium, Msi1 and Msi2 have analogous oncogenic effects. Further, comparison of Msi1/2-induced gene expression programs and transcriptome-wide analyses of Msi1/2-RNA-binding targets reveal significant functional overlap, including induction of the PDK-Akt-mTORC1 axis. Ultimately, we demonstrate that concomitant loss of function of both ...


Dielectrophoretic Capture And Genetic Analysis Of Single Neuroblastoma Cells, Erica L Carpenter, Julieann Rader, Jacob Ruden, Eric F. Rappaport, Kristen N. Hunter, Paul L. Hallberg, Kate Krystka, Peter J. O'Dwyer, Yael Mosse Jul 2014

Dielectrophoretic Capture And Genetic Analysis Of Single Neuroblastoma Cells, Erica L Carpenter, Julieann Rader, Jacob Ruden, Eric F. Rappaport, Kristen N. Hunter, Paul L. Hallberg, Kate Krystka, Peter J. O'Dwyer, Yael Mosse

BBB Major Publications

Our understanding of the diversity of cells that escape the primary tumor and seed micrometastases remains rudimentary, and approaches for studying circulating and disseminated tumor cells have been limited by low throughput and sensitivity, reliance on single parameter sorting, and a focus on enumeration rather than phenotypic and genetic characterization. Here, we utilize a highly sensitive microfluidic and dielectrophoretic approach for the isolation and genetic analysis of individual tumor cells. We employed fluorescence labeling to isolate 208 single cells from spiking experiments conducted with 11 cell lines, including 8 neuroblastoma cell lines, and achieved a capture sensitivity of 1 tumor ...


Characterization Of The Ossn Microbiome In Hiv-1 Infected Patients, Kenneth O. Simbiri, Erle S. Robertson May 2012

Characterization Of The Ossn Microbiome In Hiv-1 Infected Patients, Kenneth O. Simbiri, Erle S. Robertson

Botswana-UPenn Scholarly Publications

Purpose: Ocular surface squamous neoplasia (OSSN) is a rare cancer previously seen in elderly men. In Botswana there is an increase in OSSN and pterygia among young HIV-1 infected patients. Factors that determine the course of this cancer have not been characterized. Recent studies identified HPV, EBV, KSHV, HSV-1/2, and CMV in patient samples. We now characterize the microbiome associated with the disease that may contribute to its course.

Results: Pyrosequencing identified viruses, bacteria, fungus and parasites. Analysis of shotgun cloning sequences showed a majority of infectious agents identified by pyrosequencing.

Conclusion: HIV patients with OSSN in Botswana are ...


The Cytoskeletal Mechanisms Of Cell-Cell Junction Formation In Endothelial Cells, Matthew K. Hoelzle Dec 2011

The Cytoskeletal Mechanisms Of Cell-Cell Junction Formation In Endothelial Cells, Matthew K. Hoelzle

Publicly Accessible Penn Dissertations

Intercellular adhesions are essential for compartmentalization and integrity of tissues in an organism, cell-cell communication, and morphogenesis. The actin cytoskeleton and associated proteins play a vital role in establishing and maintaining cell-cell adhesion. However, the procedure by which cells establish adherens junctions remains largely unclear.

We investigated the dynamics of cell-cell junction formation and the corresponding architecture of the underlying cytoskeleton in cultured human umbilical vein endothelial cells (HUVECs). We show that the initial interaction between cells is mediated by protruding lamellipodia. Upon their retraction, cells maintain contact through thin bridges formed by filopodia-like protrusions connected by VE-cadherin-rich junctions.

Bridges ...


Mechanism Of Cyclin D1-Dependent Genomic Instability And Neoplastic Transformation, Laura Pontano Vaites Aug 2011

Mechanism Of Cyclin D1-Dependent Genomic Instability And Neoplastic Transformation, Laura Pontano Vaites

Publicly Accessible Penn Dissertations

Regulation of cyclin D1-dependent kinase activity is essential for cell cycle progression and DNA replication fidelity. Critically, impaired cyclin D1 phosphorylation and ubiquitin-mediated proteolysis following the G1/S transition drives neoplastic growth, suggesting that posttranslational regulation is required for cell homeostasis. Elucidation of mechanisms facilitating S-phase cyclin D1 accumulation and novel functions of nuclear cyclin D1/CDK4 kinase is critical for understanding the role of cyclin D1 in tumorigenesis. The work presented herein demonstrates that accelerated, Fbx4-dependent cyclin D1 degradation following S-phase DNA damage is essential to maintain genome stability. Furthermore, Fbx4 functions as a bona fide tumor suppressor, as ...


Role Of Rap Signaling In The Regulation Of Erk Activation And Cell-Cell Adhesion, Lisa A. Vuchak May 2011

Role Of Rap Signaling In The Regulation Of Erk Activation And Cell-Cell Adhesion, Lisa A. Vuchak

Publicly Accessible Penn Dissertations

Rap is a member of the Ras family of small GTPases. Mammalian Rap proteins regulate many biological processes including cell and matrix adhesion, migration, proliferation, cytoskeletal dynamics, cell polarity and secretion. Rap1 is activated by TSH and cAMP in thyroid cells independently of PKA. TSH regulates differentiated gene expression and proliferation. Many of these effects are mediated through PKA. There is disagreement as to whether cAMP signaling through Rap contributes to any of the cellular effects of TSH. Given that thyroid cells express high levels of B-Raf and that Rap1 activates ERK through B-Raf in many cells, we investigated whether ...


Lin28b, Let-7, And The Molecular Pathogenesis Of Colon Cancer, Catrina E. King Dec 2010

Lin28b, Let-7, And The Molecular Pathogenesis Of Colon Cancer, Catrina E. King

Publicly Accessible Penn Dissertations

Lin28b is an RNA-binding protein that inhibits biogenesis of tumor-suppressive microRNAs of the let-7 family, and is involved in induction of pluripotency. Although LIN28B has been implicated in cancer, a specific role in colon tumorigenesis has not been elucidated. We have determined that colon tumors exhibit decreased levels of mature let-7 isoforms, and that constitutive let-7 expression inhibits migration and invasion of colon cancer cells in vitro. Importantly, down-regulation of let-7a and let-7b in colon tumors correlates with increased expression of LIN28B, suggesting tumor-promoting properties of this let-7 inhibitor. In order to determine the role of LIN28B in colon cancer ...


Effects Of The Bcr-Abll Oncogene On Dna Damage And Repair, Beth A. Burke Aug 2010

Effects Of The Bcr-Abll Oncogene On Dna Damage And Repair, Beth A. Burke

Publicly Accessible Penn Dissertations

Chronic myeloid leukemia (CML) is a two-stage disease caused by the p210 BCR-ABL protein. BCR-ABL is a constitutively activated tyrosine kinase that activates signaling pathways to enhance proliferation and inhibit apoptosis. BCR-ABL kinase activity directly causes CML chronic phase, the first stage of CML, but the role of BCR-ABL in transitioning to blast crisis (BC), the second stage of disease, remains under investigation. Given that CML BC is marked by additional chromosomal abnormalities, the role of BCR-ABL in contributing to genomic instability through effects on DNA damage and DNA repair processes has been studied. We investigated what impact BCR-ABL has ...


Mechanisms Of The Downregulation Of Prolactin Receptor And Their Role In Cell Proliferation, Bentley J. Varghese May 2010

Mechanisms Of The Downregulation Of Prolactin Receptor And Their Role In Cell Proliferation, Bentley J. Varghese

Publicly Accessible Penn Dissertations

Cells react to diverse stimuli by expressing specific receptors that recognize these stimuli and initiate specific signaling pathways that enable a cell to change with the environment. Downregulation of these signaling receptors represents the most direct method for limiting the magnitude and duration of downstream signal transduction. For cell surface transmembrane receptors, ligand-stimulated endocytosis is a major mechanism by which the ability of a cell to react to a ligand is restricted. In order to investigate the downregulation of the prolactin receptor (PRLr), we investigated the mechanism and key determinants in the endocytosis and downregulation of PRLr. In Chapter 2 ...


Functions Of Dna Damage Response Factors In Lymphocyte Development And Transformation, Bu Yin May 2010

Functions Of Dna Damage Response Factors In Lymphocyte Development And Transformation, Bu Yin

Publicly Accessible Penn Dissertations

DNA double strand breaks (DSBs) can activate cell cycle checkpoints or apoptosis, and lead to genomic alterations that drive malignant transformation. The H2AX core histone variant is phosphorylated in chromatin around DSBs by kinases such as ATM and DNA-PKcs. However, how H2AX suppresses chromosome breaks and translocations in cells and prevents tumorigenesis in mice and humans is not well understood. V(D)J recombination is a genetically programmed DNA damage and repair process that assembles the variable region exons of antigen receptor genes in developing lymphocytes. Using an inducible V(D)J recombination system, I found that H2AX is phosphorylated ...


The Role Of The Transcription Factor Atf4iin Tumor Progression Under Nutrient Deprivation And Hypoxia, Jiangbin Ye May 2010

The Role Of The Transcription Factor Atf4iin Tumor Progression Under Nutrient Deprivation And Hypoxia, Jiangbin Ye

Publicly Accessible Penn Dissertations

The transcription factor ATF4 regulates the expression of mRNAs involved in amino acid metabolism, redox homeostasis and ER stress responses. Its overexpression in human solid tumors suggests an important role in tumor biology. Here we report that inhibition of ATF4 expression blocks proliferation and survival of transformed cells, despite an initial activation of cytoprotective macroautophagy. Knockdown of ATF4 significantly reduced the levels of asparagine synthetase (ASNS). Overexpression of ASNS or supplementation of asparagine in trans, reverses the proliferation block and increases survival in ATF4 knockdown cells. Both amino acid and glucose deprivation, stresses found in solid tumors, activate the upstream ...