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2017

Cancer Biology

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Articles 1 - 30 of 35

Full-Text Articles in Molecular Biology

Serine-Dependent Sphingolipid Synthesis Is A Metabolic Liability Of Aneuploid Cells, Sunyoung Hwang, H. Tobias Gustafsson, Ciara O'Sullivan, Gianna Bisceglia, Xinhe Huang, Christian Klose, Andrej Schevchenko, Robert C. Dickson, Paola Cavaliere, Noah Dephoure, Eduardo M. Torres Dec 2017

Serine-Dependent Sphingolipid Synthesis Is A Metabolic Liability Of Aneuploid Cells, Sunyoung Hwang, H. Tobias Gustafsson, Ciara O'Sullivan, Gianna Bisceglia, Xinhe Huang, Christian Klose, Andrej Schevchenko, Robert C. Dickson, Paola Cavaliere, Noah Dephoure, Eduardo M. Torres

University of Massachusetts Medical School Faculty Publications

Aneuploidy disrupts cellular homeostasis. However, the molecular mechanisms underlying the physiological responses and adaptation to aneuploidy are not well understood. Deciphering these mechanisms is important because aneuploidy is associated with diseases, including intellectual disability and cancer. Although tumors and mammalian aneuploid cells, including several cancer cell lines, show altered levels of sphingolipids, the role of sphingolipids in aneuploidy remains unknown. Here, we show that ceramides and long-chain bases, sphingolipid molecules that slow proliferation and promote survival, are increased by aneuploidy. Sphingolipid levels are tightly linked to serine synthesis, and inhibiting either serine or sphingolipid synthesis can specifically impair the fitness ...


Metabolic Reprogramming Of Pancreatic Ductal Adenocarcinoma Cells In Response To Chronic Low Ph Stress, Jaime Abrego Dec 2017

Metabolic Reprogramming Of Pancreatic Ductal Adenocarcinoma Cells In Response To Chronic Low Ph Stress, Jaime Abrego

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of all cancers with a 5-year survival rate of only 8.2%. This is because PDAC is diagnosed in its advanced stages and is characterized by radio and chemotherapy resistance. Aggressiveness of PDAC tumors is attributed to its high metabolic phenotype, which is characterized by increased glycolysis rate and lactate secretion, while oxidative metabolism is reduced. These metabolic features are required to fulfill the biosynthetic demands of proliferating PDAC cells. However, this increase in metabolic activity results in acidification of the extracellular space because the dense fibrotic stroma of PDAC tumors ...


The Alpha6beta4 Integrin Promotes Resistance To Ferroptosis, Caitlin W. Brown, John J. Amante, Hira Lal Goel, Arthur M. Mercurio Dec 2017

The Alpha6beta4 Integrin Promotes Resistance To Ferroptosis, Caitlin W. Brown, John J. Amante, Hira Lal Goel, Arthur M. Mercurio

UMass Metabolic Network Publications

Increases in lipid peroxidation can cause ferroptosis, a form of cell death triggered by inhibition of glutathione peroxidase 4 (GPX4), which catalyzes the reduction of lipid peroxides and is a target of ferroptosis inducers, such as erastin. The alpha6beta4 integrin protects adherent epithelial and carcinoma cells from ferroptosis induced by erastin. In addition, extracellular matrix (ECM) detachment is a physiologic trigger of ferroptosis, which is evaded by alpha6beta4. The mechanism that enables alpha6beta4 to evade ferroptosis involves its ability to protect changes in membrane lipids that are proferroptotic. Specifically, alpha6beta4-mediated activation of Src and STAT3 suppresses expression of ACSL4, an ...


Characterization Of Notch1 And Pi3k-Pten-Akt/Mtor Pathway Interaction In Head And Neck Squamous Cell Carcinoma, Kyriante' Henry Dec 2017

Characterization Of Notch1 And Pi3k-Pten-Akt/Mtor Pathway Interaction In Head And Neck Squamous Cell Carcinoma, Kyriante' Henry

UT GSBS Dissertations and Theses (Open Access)

Head and neck squamous cell carcinoma (HNSCC) affects various mucosal sites of the upper aerodigestive tract, including the nasal and oral cavities, the nasopharynx, and the oropharynx. More than five hundred thousand new cases of HNSCC occurred in 2011 alone, with 50,000 reported cases in the United States. This trend made HNSCC the seventh most common non-skin cancer worldwide (Ferlay et al., 2015). Although significant epidemiological and pathological advancements have been made, survival rates have not improved much over the last 40 years, leaving a mortality rate that remains at approximately 50%. An unbiased drug screen demonstrated that HNSCC ...


Bivalent Epigenetic Control Of Oncofetal Gene Expression In Cancer, Sayyed K. Zaidi, Seth E. Frietze, Jonathan A. Gordon, Jessica L. Heath, Terri Messier, Deli Hong, Joseph R. Boyd, Mingu Kang, Anthony N. Imbalzano, Jane B. Lian, Janet L. Stein, Gary S. Stein Nov 2017

Bivalent Epigenetic Control Of Oncofetal Gene Expression In Cancer, Sayyed K. Zaidi, Seth E. Frietze, Jonathan A. Gordon, Jessica L. Heath, Terri Messier, Deli Hong, Joseph R. Boyd, Mingu Kang, Anthony N. Imbalzano, Jane B. Lian, Janet L. Stein, Gary S. Stein

UMass Metabolic Network Publications

Multiple mechanisms of epigenetic control that include DNA methylation, histone modification, noncoding RNAs, and mitotic gene bookmarking play pivotal roles in stringent gene regulation during lineage commitment and maintenance. Experimental evidence indicates that bivalent chromatin domains, i.e., genome regions that are marked by both H3K4me3 (activating) and H3K27me3 (repressive) histone modifications, are a key property of pluripotent stem cells. Bivalency of developmental genes during the G1 phase of the pluripotent stem cell cycle contributes to cell fate decisions. Recently, some cancer types have been shown to exhibit partial recapitulation of bivalent chromatin modifications that are lost along with pluripotency ...


A Role For Tau Protein In Maintaining Ribosomal Dna Stability And Cytidine Deaminase-Deficient Cell Survival, Elias Bou Samra, Geraldine Buhagiar-Labarchede, Christelle Machon, Jerome Guitton, Rosine Onclercq-Delic, Michael R. Green, Olivier Alibert, Claude Gazin, Xavier Veaute, Mounira Amor-Gueret Sep 2017

A Role For Tau Protein In Maintaining Ribosomal Dna Stability And Cytidine Deaminase-Deficient Cell Survival, Elias Bou Samra, Geraldine Buhagiar-Labarchede, Christelle Machon, Jerome Guitton, Rosine Onclercq-Delic, Michael R. Green, Olivier Alibert, Claude Gazin, Xavier Veaute, Mounira Amor-Gueret

Open Access Articles

Cells from Bloom's syndrome patients display genome instability due to a defective BLM and the downregulation of cytidine deaminase. Here, we use a genome-wide RNAi-synthetic lethal screen and transcriptomic profiling to identify genes enabling BLM-deficient and/or cytidine deaminase-deficient cells to tolerate constitutive DNA damage and replication stress. We found a synthetic lethal interaction between cytidine deaminase and microtubule-associated protein Tau deficiencies. Tau is overexpressed in cytidine deaminase-deficient cells, and its depletion worsens genome instability, compromising cell survival. Tau is recruited, along with upstream-binding factor, to ribosomal DNA loci. Tau downregulation decreases upstream binding factor recruitment, ribosomal RNA synthesis ...


Exploring Biological Heterogeneity And Its Consequences At Tissue And Cellular Scales Through Mathematical And Computational Modeling, Romica Kerketta Sep 2017

Exploring Biological Heterogeneity And Its Consequences At Tissue And Cellular Scales Through Mathematical And Computational Modeling, Romica Kerketta

Biomedical Sciences ETDs

This dissertation explores the effects of heterogeneity across different biological scales in cancer as well as normal cells. At the tissue scale, we investigated the variability present in the tumor microenvironment and its effect on patient chemotherapeutic outcomes using a mathematical model of drug transport. We found that parameters such as tumor blood perfusion and radius of blood vessel had an impact on the tumor cytotoxicity. This indicated that the physical microenvironment of the tumor is an important regulator of the tumor response to chemotherapy. At the cellular scale, we investigated the heterogeneity present on the membrane landscape of ErbB2 ...


A Dual Role Of Caspase-8 In Triggering And Sensing Proliferation-Associated Dna Damage, A Key Determinant Of Liver Cancer Development, Yannick Boege, Roger J. Davis, Achim Weber Sep 2017

A Dual Role Of Caspase-8 In Triggering And Sensing Proliferation-Associated Dna Damage, A Key Determinant Of Liver Cancer Development, Yannick Boege, Roger J. Davis, Achim Weber

UMass Metabolic Network Publications

Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels of hepatocyte apoptosis determine and predict subsequent hepatocarcinogenesis. Proliferation-associated DNA damage is sensed by a complex comprising caspase-8, FADD, c-FLIP, and a kinase-dependent function of RIPK1. This platform requires a non-apoptotic function of caspase-8, but no caspase-3 or caspase-8 cleavage. It may represent a DNA damage-sensing mechanism in ...


Critical Role For Arginase 2 In Obesity-Associated Pancreatic Cancer, Tamara Zaytouni, Pei-Yun Tsai, Daniel S. Hitchcock, Cory D. Dubois, Elizaveta Freinkman, Lin Lin, Vicente Morales-Oyarvide, Patrick J. Lenehan, Brian M. Wolpin, Mari Mino-Kenudson, Eduardo M. Torres, Nicholas Stylopoulos, Clary B. Clish, Nada Y. Kalaany Aug 2017

Critical Role For Arginase 2 In Obesity-Associated Pancreatic Cancer, Tamara Zaytouni, Pei-Yun Tsai, Daniel S. Hitchcock, Cory D. Dubois, Elizaveta Freinkman, Lin Lin, Vicente Morales-Oyarvide, Patrick J. Lenehan, Brian M. Wolpin, Mari Mino-Kenudson, Eduardo M. Torres, Nicholas Stylopoulos, Clary B. Clish, Nada Y. Kalaany

UMass Metabolic Network Publications

Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDA). Despite recent identification of metabolic alterations in this lethal malignancy, the metabolic dependencies of obesity-associated PDA remain unknown. Here we show that obesity-driven PDA exhibits accelerated growth and a striking transcriptional enrichment for pathways regulating nitrogen metabolism. We find that the mitochondrial form of arginase (ARG2), which hydrolyzes arginine into ornithine and urea, is induced upon obesity, and silencing or loss of ARG2 markedly suppresses PDA. In vivo infusion of (15)N-glutamine in obese mouse models of PDA demonstrates enhanced nitrogen flux into the urea cycle and infusion of ...


Preclinical Development Of Therapeutic Strategies Against Triple-Negative And Inflammatory Breast Cancer, Angie M. Torres-Adorno Aug 2017

Preclinical Development Of Therapeutic Strategies Against Triple-Negative And Inflammatory Breast Cancer, Angie M. Torres-Adorno

UT GSBS Dissertations and Theses (Open Access)

Triple-negative (TNBC) and inflammatory (IBC) breast cancer are the most aggressive forms of breast cancer, accounting for 20% and 10% of cancer-related deaths, respectively. Among IBC cases, 30% are additionally classified with TNBC molecular pathology, a diagnosis that significantly worsens patient’s prognosis. The current lack of TNBC and IBC molecular understanding prevents the development of effective therapeutic strategies. To identify effective treatments, we explored aberrant apoptosis pathways and cell membrane fluidity as novel therapeutic targets.

We first identified an effective therapeutic strategy against TNBC and IBC by pro-apoptotic protein NOXA-mediated inhibition of the anti-apoptotic protein MCL1 following inhibition of ...


Molecular And Biochemical Studies Of Several Novel Estrogen Receptor Alpha-Interacting Proteins In Breast Cancer Cells, Ahmed Edan Dhamad Aug 2017

Molecular And Biochemical Studies Of Several Novel Estrogen Receptor Alpha-Interacting Proteins In Breast Cancer Cells, Ahmed Edan Dhamad

Theses and Dissertations

Breast cancer is the second leading cause of cancer-related death in women, and approximately 70% of incidences are estrogen receptor (ER)-positive breast cancer. ERα and its interacting proteins play a key role in the development and progression of breast cancer. However, how ERα regulates its target gene expression and hence cell proliferation is not fully understood. To enhance our understanding of the molecular mechanism by which ERα regulates gene expression, we used a quantitative proteomic method to identify cellular proteins that interact with ERα. The first group of proteins that were identified to associate with ERα are heat shock ...


The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers Aug 2017

The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers

Electronic Theses and Dissertations

Primordial germ cells (PGCs) are hypothesized to deposit hematopoietic stem cells (HSCs) along their migration route through the embryo during the early stages of embryogenesis. PGCs also undergo global chromatin remodeling, including the erasure and reestablishment of genomic imprints, during this migration. While PGCs do not spontaneously form teratomas, their malignant development into germ cell tumors (GCTs) in vivo is often accompanied by the retention of hypomethylation at the IGF2-H19 imprinting control differentially methylated region (DMR). Previous studies in bimaternal embryos determined that proper genomic imprinting at two paternally imprinted loci was necessary for their growth and development: Igf2-H19 and ...


Jnks Function As Cdk4-Activating Kinases By Phosphorylating Cdk4 And P21, B. Colleoni, S. Paternot, J. M. Pita, X. Bisteau, K. Coulonval, Roger J. Davis, E. Raspe, P. P. Roger Jul 2017

Jnks Function As Cdk4-Activating Kinases By Phosphorylating Cdk4 And P21, B. Colleoni, S. Paternot, J. M. Pita, X. Bisteau, K. Coulonval, Roger J. Davis, E. Raspe, P. P. Roger

Open Access Articles

Cyclin D-CDK4/6 are the first cyclin-dependent kinase (CDK) complexes to be activated by mitogenic/oncogenic pathways. They have a central role in the cell multiplication decision and in its deregulation in cancer cells. We identified T172 phosphorylation of CDK4 rather than cyclin D accumulation as the distinctly regulated step determining CDK4 activation. This finding challenges the view that the only identified metazoan CDK-activating kinase, cyclin H-CDK7-Mat1 (CAK), which is constitutively active, is responsible for the activating phosphorylation of all cell cycle CDKs. We previously showed that T172 phosphorylation of CDK4 is conditioned by an adjacent proline (P173), which is ...


Mirna-124-3p Reduces Cell Viability In Cisplatin Resistant Neuroblastoma Cell Models., John Christopher Nolan Jul 2017

Mirna-124-3p Reduces Cell Viability In Cisplatin Resistant Neuroblastoma Cell Models., John Christopher Nolan

PhD theses

Neuroblastoma is a highly heterogeneous disease, responsible for 15 % of paediatric cancer deaths. Acquired drug resistance is a major obstacle in high risk neuroblastoma, making the elucidation of mechanisms in development and modulation of drug resistance essential.

Three drug-resistant models, KellyCis83, CHP212Cis100 and SK-N-ASCis24 were developed previously to elucidate mechanisms involved in cisplatin resistance development.

Cisplatin resistance induces phenotypic changes in neuroblastoma. The aim of this work was to characterise phenotypic and proteomic changes and validate a miRNA capable of regulating the expression of up-regulated genes from proteomic analysis of cisplatin resistant sub-lines.

Proteomic profiling was carried out on the ...


The Effect Of Target-Specific Biomolecules In Breast Cancer, Mohannad Garoub Jun 2017

The Effect Of Target-Specific Biomolecules In Breast Cancer, Mohannad Garoub

FIU Electronic Theses and Dissertations

Cancer is the second leading cause of mortality in the United States and the World, therefore, early effective prevention, diagnosis, and therapy is needed. Estrogens play a major role in the initiation and progression of breast cancer. Elevated lifetime exposure to estrogens is associated with an increased risk of developing breast cancer. Estrogens through influencing mitochondria contribute to estrogen induced breast carcinogenesis; however, the exact mitochondrial mechanisms underlying the estrogen carcinogenic effect in breast tissue are not clearly understood. For this dissertation, the mitotoxic and cytotoxic effects of triphenylphosphonium cation (TPP) and Origanum majorana organic extract (OME) as well as ...


An Embryonic Stem Cell-Specific Nurd Complex Functions Through Interaction With Wdr5, Ly-Sha Ee, Kurtis N. Mccannell, Yang Tang, Nancy Fernandes, W. Rod Hardy, Michael R. Green, Feixia Chu, Thomas G. Fazzio Jun 2017

An Embryonic Stem Cell-Specific Nurd Complex Functions Through Interaction With Wdr5, Ly-Sha Ee, Kurtis N. Mccannell, Yang Tang, Nancy Fernandes, W. Rod Hardy, Michael R. Green, Feixia Chu, Thomas G. Fazzio

Open Access Articles

The Nucleosome Remodeling and Deacetylase (NuRD) complex is a chromatin regulatory complex that functions as a transcriptional co-repressor in metazoans. The NuRD subunit MBD3 is essential for targeting and assembly of a functional NuRD complex as well as embryonic stem cell (ESC) pluripotency. Three MBD3 isoforms (MBD3A, MBD3B, and MBD3C) are expressed in mouse. Here, we find that the MBD3C isoform contains a unique 50-amino-acid N-terminal region that is necessary for MBD3C to specifically interact with the histone H3 binding protein WDR5. Domain analyses of WDR5 reveal that the H3 binding pocket is required for interaction with MBD3C. We find ...


Jak/Stat Pathway Inhibition Overcomes Il7-Induced Glucocorticoid Resistance In A Subset Of Human T-Cell Acute Lymphoblastic Leukemias, C. Delgado-Martin, L. K. Meyer, B. J. Huang, M. S. Zinter, J. V. Nguyen, G. A. Smith, J. Taunton, S. S. Winter, Justine R. Roderick, Michelle A. Kelliher, T. M. Horton, B. L. Wood, D. T. Teachey, M. L. Hermiston May 2017

Jak/Stat Pathway Inhibition Overcomes Il7-Induced Glucocorticoid Resistance In A Subset Of Human T-Cell Acute Lymphoblastic Leukemias, C. Delgado-Martin, L. K. Meyer, B. J. Huang, M. S. Zinter, J. V. Nguyen, G. A. Smith, J. Taunton, S. S. Winter, Justine R. Roderick, Michelle A. Kelliher, T. M. Horton, B. L. Wood, D. T. Teachey, M. L. Hermiston

UMass Metabolic Network Publications

While outcomes for children with T-cell acute lymphoblastic leukemia (T-ALL) have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid (GC) resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor (ETP) T-ALLs as well as in a subset of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling ...


Cannabinoid Receptor 2 And C-X-C Chemokine Receptor 4 Interact To Abrogate Cxcl12-Mediated Cellular Response, Christopher James Coke May 2017

Cannabinoid Receptor 2 And C-X-C Chemokine Receptor 4 Interact To Abrogate Cxcl12-Mediated Cellular Response, Christopher James Coke

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The expression of C-X-C Chemokine Receptor 4 (CXCR4) has been correlated with increased metastatic potential of cancer cells. CXCR4 increases tumor malignancy by encouraging tumors cells to migrate to distal organs expressing its cognate ligand, CXCL12, facilitating metastasis. Thus, targeting the CXCR4/CXCL12 signaling axis provides a good strategy to inhibit the metastatic spread of tumor cells and slow cancer progression. Various studies suggest that cannabis may have anti-proliferative as well as anti-metastatic properties, though a biochemical mechanism describing how this occurs has yet to be discovered. Our lab has confirmed that agonist-bound CXCR4 and agonist-bound Cannabinoid Receptor 2 (CB2 ...


Differential Involvement Of The Microtubule Cytoskeleton In Insulin Receptor Substrate 1 (Irs-1) And Irs-2 Signaling To Akt Determines The Response To Microtubule Disruption In Breast Carcinoma Cells, Jose Mercado-Matos, Jennifer L. Clark, Andrew J. Piper, Jenny Janusis, Leslie M. Shaw May 2017

Differential Involvement Of The Microtubule Cytoskeleton In Insulin Receptor Substrate 1 (Irs-1) And Irs-2 Signaling To Akt Determines The Response To Microtubule Disruption In Breast Carcinoma Cells, Jose Mercado-Matos, Jennifer L. Clark, Andrew J. Piper, Jenny Janusis, Leslie M. Shaw

UMass Metabolic Network Publications

The insulin receptor substrate (IRS) proteins serve as essential signaling intermediates for the activation of PI3K by both the insulin-like growth factor 1 receptor (IGF-1R) and its close family member, the insulin receptor (IR). Although IRS-1 and IRS-2 share significant homology, they regulate distinct cellular responses downstream of these receptors and play divergent roles in breast cancer. To investigate the mechanism by which signaling through IRS-1 and IRS-2 results in differential outcomes, we assessed the involvement of the microtubule cytoskeleton in IRS-dependent signaling. Treatment with drugs that either stabilize or disrupt microtubules reveal that an intact microtubule cytoskeleton contributes to ...


Chloramidine/Bisindolylmaleimide-I-Mediated Inhibition Of Exosome And Microvesicle Release And Enhanced Efficacy Of Cancer Chemotherapy, Uchini S. Kosgodage, Rita P. Trindade, Paul R. Thompson, Jameel M. Inal, Sigrun Lange May 2017

Chloramidine/Bisindolylmaleimide-I-Mediated Inhibition Of Exosome And Microvesicle Release And Enhanced Efficacy Of Cancer Chemotherapy, Uchini S. Kosgodage, Rita P. Trindade, Paul R. Thompson, Jameel M. Inal, Sigrun Lange

Open Access Articles

Microvesicle (MV) release from tumour cells influences drug retention, contributing to cancer drug resistance. Strategically regulating MV release may increase drug retention within cancer cells and allow for lower doses of chemotherapeutic drugs. The contribution of exosomes to drug retention still remains unknown. Potential exosome and MV (EMV) biogenesis inhibitors, tested on human prostate cancer (PC3) cells for their capacity to inhibit EMV release, were also tested on PC3 and MCF-7 (breast cancer) cells for improving chemotherapy. Agents inhibiting EMV release most significantly, whilst maintaining cell viability, were chloramidine (Cl-amidine; 50 microM) and bisindolylmaleimide-I (10 microM). Apoptosis mediated by the ...


Rna-Sequencing Reveals Direct Targets Of Tumor Suppressor Mir-203 In Human Mammary Epithelial Cells, Alexander P. Boardman, Victoria E. Pedanou, Tessa M. Simone, Michael R. Green May 2017

Rna-Sequencing Reveals Direct Targets Of Tumor Suppressor Mir-203 In Human Mammary Epithelial Cells, Alexander P. Boardman, Victoria E. Pedanou, Tessa M. Simone, Michael R. Green

Senior Scholars Program

Background: Breast cancer is the leading cause of cancer-related mortality in women worldwide. Since a significant portion of cases present with or progress to metastatic disease, furthering our understanding of metastasis is critical to develop better treatments. Epithelial cells maintain contact with the extracellular matrix (ECM) predominantly via integrin engagement, a process required for tissue integrity and barrier function. In non-transformed cells, loss of ECM adhesion promotes a specialized form of programmed cell death, anoikis. In order for efficient metastasis to occur, breast tumor cells must evade anoikis. miR-203, known to be down-regulated in several cancers, was found by our ...


A Review Of The Signal Transduction Pathways Involved In Epithelial Mesenchymal Transition Induced In Breast Cancer Metastasis And Their Cross-Talks, Kasey Cervantes '17 May 2017

A Review Of The Signal Transduction Pathways Involved In Epithelial Mesenchymal Transition Induced In Breast Cancer Metastasis And Their Cross-Talks, Kasey Cervantes '17

Independent Study

Epithelial-Mesenchymal Transition (EMT) is a biological process utilized by epithelial cells to transform into motile mesenchymal cells, initiating metastasis in cancer. EMT is also utilized during development and wound healing [10]. This process allows for cancerous cells to detach themselves from their primary tumor and invade normal tissue in preferred organ sites, forming secondary tumors called metastases. Metastasis is very important in the progression of cancer in patients as it the process responsible for the mortality of patients through the collection of metastases that effect vital organs like the brain, lung, or immune system. The most common metastases for malignant ...


Non-Coding Rnas Identify The Intrinsic Molecular Subtypes Of Muscle-Invasive Bladder Cancer, Andrea E. Ochoa May 2017

Non-Coding Rnas Identify The Intrinsic Molecular Subtypes Of Muscle-Invasive Bladder Cancer, Andrea E. Ochoa

UT GSBS Dissertations and Theses (Open Access)

NON-CODING RNAS IDENTIFY THE INTRINSIC MOLECULAR SUBTYPES OF MUSCLE-INVASIVE BLADDER CANCER

Andrea Elizabeth Ochoa, B.S.

Advisory Professors: David J. McConkey, Ph.D. and Joya Chandra, Ph.D.

There has been a recent explosion of genomics data in muscle-invasive bladder cancer (MIBC) to better understand the underlying biology of the disease that leads to the high amount of heterogeneity that is seen clinically. These studies have identified relatively stable intrinsic molecular subtypes of MIBC that show similarities to the basal and luminal subtypes of breast cancer. However, previous studies have primarily focused on protein-coding genes or DNA mutations/alterations.

There ...


Mechanism Of Lck Activation In Driving Leukemia Cell Proliferation, Hannah E. Dobson May 2017

Mechanism Of Lck Activation In Driving Leukemia Cell Proliferation, Hannah E. Dobson

Senior Honors Projects

Leukemia is a type of cancer that develops in blood-forming tissues of the immune system. These tissues can include the bone marrow or sites within the lymphatic system such as the lymph nodes. Leukemia progresses from a mutational event within a white blood cell. Often this mutation alters the cell’s normal life cycle, resulting in uninhibited cell division and growth. With this uncontrolled cell proliferation, mutated white blood cells accumulate and begin interfering with the functioning of healthy cells.

Scientists are unsure of the exact mechanisms required for leukemia development. However, recently scientists identified four characteristic mutations in the ...


Runx1 And Breast Cancer, Jose Mercado-Matos, Asia N. Matthew-Onabanjo, Leslie M. Shaw Apr 2017

Runx1 And Breast Cancer, Jose Mercado-Matos, Asia N. Matthew-Onabanjo, Leslie M. Shaw

UMass Metabolic Network Publications

News on: Runx1 stabilizes the mammary epithelial cell phenotype and prevents epithelial to mesenchymal transition, by Hong et al. Oncotarget. 2017; 8:17610-27. doi: 10.18632/oncotarget.15381.


Mammalian Swi/Snf Enzymes And The Epigenetics Of Tumor Cell Metabolic Reprogramming, Jeffrey A. Nickerson, Qiong Wu, Anthony N. Imbalzano Apr 2017

Mammalian Swi/Snf Enzymes And The Epigenetics Of Tumor Cell Metabolic Reprogramming, Jeffrey A. Nickerson, Qiong Wu, Anthony N. Imbalzano

UMass Metabolic Network Publications

Tumor cells reprogram their metabolism to survive and grow in a challenging microenvironment. Some of this reprogramming is performed by epigenetic mechanisms. Epigenetics is in turn affected by metabolism; chromatin modifying enzymes are dependent on substrates that are also key metabolic intermediates. We have shown that the chromatin remodeling enzyme Brahma-related gene 1 (BRG1), an epigenetic regulator, is necessary for rapid breast cancer cell proliferation. The mechanism for this requirement is the BRG1-dependent transcription of key lipogenic enzymes and regulators. Reduction in lipid synthesis lowers proliferation rates, which can be restored by palmitate supplementation. This work has established BRG1 as ...


The Effects Of Acetylenic Tricyclic Bis-(Cyano Enone) On Cell Migration, Eddie Chan Feb 2017

The Effects Of Acetylenic Tricyclic Bis-(Cyano Enone) On Cell Migration, Eddie Chan

Electronic Thesis and Dissertation Repository

Although cancer survival rates have significantly improved over the past few decades, the improvements are primarily due to early diagnosis and inhibiting cancer growth. Limited progress has been made in the treatment of cancer metastasis, which contributes to 90% of cancer related deaths, and therapeutic agents targeting the various aspects of metastasis are lacking. One potential approach is to utilize small pharmacological compounds to inhibit tumour cell motility, as a strategy against tumour cell migration, invasion, and metastasis. The acetylenic tricyclic bis-(cyano enone), TBE-31, has been shown to be a promising chemopreventative compound. However, its effects on cell migration ...


Engineering Fret Biosensors For Microrna Presence/Absence Analysis, Nicholas E. Larkey, Sean M. Burrows Feb 2017

Engineering Fret Biosensors For Microrna Presence/Absence Analysis, Nicholas E. Larkey, Sean M. Burrows

Biomedical Engineering Western Regional Conference

No abstract provided.


Oncogenic Nelfe Enhances Myc-Induced Hepatocellular Carcinogenesis, Hien Dang, Atsushi Takai, Marshonna Forgues, Yosawat Pomyen, Haiwei Mou, Wen Xue, Debashish Ray, Kevn Ha, Quiad Morris, Timothy Hughes, Xin Wei Wang Jan 2017

Oncogenic Nelfe Enhances Myc-Induced Hepatocellular Carcinogenesis, Hien Dang, Atsushi Takai, Marshonna Forgues, Yosawat Pomyen, Haiwei Mou, Wen Xue, Debashish Ray, Kevn Ha, Quiad Morris, Timothy Hughes, Xin Wei Wang

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.


Hepatocyte-Specific Deletion Of Tristetraprolin Family Of Rna Binding Proteins Result In The Development Of Hepatocellular Carcinomas, Sonika Patial Jan 2017

Hepatocyte-Specific Deletion Of Tristetraprolin Family Of Rna Binding Proteins Result In The Development Of Hepatocellular Carcinomas, Sonika Patial

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.