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Metabolism

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Articles 1 - 26 of 26

Full-Text Articles in Cancer Biology

Phosphorylation Impairs Dicer1 Function To Accelerate Aging And Tumorigenesis In Vivo, Neeraj Aryal May 2018

Phosphorylation Impairs Dicer1 Function To Accelerate Aging And Tumorigenesis In Vivo, Neeraj Aryal

UT GSBS Dissertations and Theses (Open Access)

Altered DICER1 protein levels are associated with developmental disorders, infertility, macular degenerative blindness, aging, and cancer in humans. Recently, post-translational regulation of Dicer1 via phosphorylation has been described in C. elegans. Oscillation of Dicer1 phosphorylation to regulate its activity is essential for germ cell development and embryogenesis in worms. These observations led us to posit that Dicer1 protein levels and activity are under tight regulation for normal mammalian homeostasis. To test whether phosphorylation of Dicer1 regulates its activity in mammals, I generated phospho-mimetic knock-in mouse models by replacing Serines 1712 and 1836 with Aspartic acids individually or together (dual phosphorylation ...


Pyruvate Kinase Isoform M2 Influences Autophagy And Related Processes In Hepatocellular Carcinoma Cells, Matthew Lin May 2018

Pyruvate Kinase Isoform M2 Influences Autophagy And Related Processes In Hepatocellular Carcinoma Cells, Matthew Lin

University Scholar Projects

Hepatocellular carcinoma (HCC) is the most common form of liver cancer that affects ~14 million people in the world. Like all cancers, HCC is a disease that arises from unstinted cellular growth initiated by genetic alterations, metabolic changes, and dysregulation in key cellular pathways. Of interest is the relationship between metabolism and cell proliferation/degradation for therapeutic targeting. Pyruvate kinase M2 is a dimeric, glycolytically inactive isoform of the final enzyme involved in glycolysis, that is often upregulated in cancerous tissue. It is thought that the enzymatic function of PKM2 outside of glycolysis contributes to the biosynthesis of anabolic intermediates ...


Pkm2 Influences The Metabolic Fate Of Butyrate In Colorectal Cancer Cells, Megan Louise Pence May 2018

Pkm2 Influences The Metabolic Fate Of Butyrate In Colorectal Cancer Cells, Megan Louise Pence

Chancellor’s Honors Program Projects

No abstract provided.


Pre-Diagnostic Biomarkers Of Metabolic Dysregulation And Cancer Mortality, Tomi Akinyemiju, Justin Xavier Moore, Suzanne E. Judd, Maria Pisu, Michael Goodman, Virginia J. Howard, Leann Long, Monika Safford, Susan C. Gilchrist, Mary Cushman Mar 2018

Pre-Diagnostic Biomarkers Of Metabolic Dysregulation And Cancer Mortality, Tomi Akinyemiju, Justin Xavier Moore, Suzanne E. Judd, Maria Pisu, Michael Goodman, Virginia J. Howard, Leann Long, Monika Safford, Susan C. Gilchrist, Mary Cushman

Epidemiology Faculty Publications

INTRODUCTION: The obesogenic milieu is a pro-tumorigenic environment that promotes tumor initiation, angiogenesis and metastasis. In this prospective cohort, we examined the association between pre-diagnostic metabolic biomarkers, plasma adiponectin, resistin, leptin and lipoprotein (a), and the risk of cancer mortality.

METHODS: Prospective data was obtained from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort of Blacks and Whites followed from 2003 through 2012 for cancer mortality. We determined the association between metabolism biomarkers (log-transformed and tertiles) and risk of cancer mortality using Cox Proportional Hazards models with robust sandwich estimators to calculate the 95% confidence intervals (CIs ...


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 ...


Metformin And Temozolomide, A Synergic Option To Overcome Resistance In Glioblastoma Multiforme Models, Silvia Valtorta, Alessia Lo. Dico, Isabella Raccagni, Daniela Gaglio, Sara Belloli, Letterio S. Politi, Cristina Martelli, Cecilia Diceglie, Marcella Bonanomi, Giulia Ercoli, Valentina Vaira, Luisa Ottobrini, Rosa Maria Moresco Dec 2017

Metformin And Temozolomide, A Synergic Option To Overcome Resistance In Glioblastoma Multiforme Models, Silvia Valtorta, Alessia Lo. Dico, Isabella Raccagni, Daniela Gaglio, Sara Belloli, Letterio S. Politi, Cristina Martelli, Cecilia Diceglie, Marcella Bonanomi, Giulia Ercoli, Valentina Vaira, Luisa Ottobrini, Rosa Maria Moresco

Radiology Publications and Presentations

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with poor survival. Cytoreduction in association with radiotherapy and temozolomide (TMZ) is the standard therapy, but response is heterogeneous and life expectancy is limited. The combined use of chemotherapeutic agents with drugs targeting cell metabolism is becoming an interesting therapeutic option for cancer treatment. Here, we found that metformin (MET) enhances TMZ effect on TMZ-sensitive cell line (U251) and overcomes TMZ-resistance in T98G GBM cell line. In particular, combined-treatment modulated apoptosis by increasing Bax/Bcl-2 ratio, and reduced Reactive Oxygen Species (ROS) production. We also observed that MET associated with ...


Loss Of Fructose-1,6-Bisphosphatase Induces Glycolysis And Promotes Apoptosis Resistance Of Cancer Stem-Like Cells: An Important Role In Hexavalent Chromium-Induced Carcinogenesis, Jin Dai, Yanli Ji, Wei Wang, Donghern Kim, Leonard Yenwong Fai, Lei Wang, Jia Luo, Zhuo Zhang Sep 2017

Loss Of Fructose-1,6-Bisphosphatase Induces Glycolysis And Promotes Apoptosis Resistance Of Cancer Stem-Like Cells: An Important Role In Hexavalent Chromium-Induced Carcinogenesis, Jin Dai, Yanli Ji, Wei Wang, Donghern Kim, Leonard Yenwong Fai, Lei Wang, Jia Luo, Zhuo Zhang

Toxicology and Cancer Biology Faculty Publications

Hexavalent chromium (Cr(VI)) compounds are confirmed human carcinogens for lung cancer. Our previous studies has demonstrated that chronic exposure of human bronchial epithelial BEAS-2B cells to low dose of Cr(VI) causes malignant cell transformation. The acquisition of cancer stem cell-like properties is involved in the initiation of cancers. The present study has observed that a small population of cancer stem-like cells (BEAS-2B-Cr-CSC) exists in the Cr(VI)-transformed cells (BEAS-2B-Cr). Those BEAS-2B-Cr-CSC exhibit extremely reduced capability of generating reactive oxygen species (ROS) and apoptosis resistance. BEAS-2B-Cr-CSC are metabolic inactive as evidenced by reductions in oxygen consumption, glucose uptake ...


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 ...


Alcohol And Cancer: Mechanisms And Therapies, Anuradha Ratna, Pranoti Mandrekar Aug 2017

Alcohol And Cancer: Mechanisms And Therapies, Anuradha Ratna, Pranoti Mandrekar

Open Access Articles

Several scientific and clinical studies have shown an association between chronic alcohol consumption and the occurrence of cancer in humans. The mechanism for alcohol-induced carcinogenesis has not been fully understood, although plausible events include genotoxic effects of acetaldehyde, cytochrome P450 2E1 (CYP2E1)-mediated generation of reactive oxygen species, aberrant metabolism of folate and retinoids, increased estrogen, and genetic polymorphisms. Here, we summarize the impact of alcohol drinking on the risk of cancer development and potential underlying molecular mechanisms. The interactions between alcohol abuse, anti-tumor immune response, tumor growth, and metastasis are complex. However, multiple studies have linked the immunosuppressive effects ...


Exploring Cancer Metabolism Using Stable Isotope-Resolved Metabolomics (Sirm), Ronald C. Bruntz, Andrew N. Lane, Richard M. Higashi, Teresa W. -M. Fan Jun 2017

Exploring Cancer Metabolism Using Stable Isotope-Resolved Metabolomics (Sirm), Ronald C. Bruntz, Andrew N. Lane, Richard M. Higashi, Teresa W. -M. Fan

Center for Environmental and Systems Biochemistry Faculty Publications

Metabolic reprogramming is a hallmark of cancer. The changes in metabolism are adaptive to permit proliferation, survival, and eventually metastasis in a harsh environment. Stable isotope-resolved metabolomics (SIRM) is an approach that uses advanced approaches of NMR and mass spectrometry to analyze the fate of individual atoms from stable isotope-enriched precursors to products to deduce metabolic pathways and networks. The approach can be applied to a wide range of biological systems, including human subjects. This review focuses on the applications of SIRM to cancer metabolism and its use in understanding drug actions.


Characterization Of Zic2 As An Oncoprotein In Prostate Cancer, Keira C. Davis May 2017

Characterization Of Zic2 As An Oncoprotein In Prostate Cancer, Keira C. Davis

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

The field of prostate cancer research is in need of biological markers that predict which cancers do not need treatment, those that can be treated successfully with a localized treatment and more specific cases in which patients are likely to have an aggressive form of cancer that will require more aggressive surgical and chemotherapeutic treatments. ZIC2 is one of five members of a family of proteins that play critical roles in neural crest and mesoderm growth in normal embryonic brain development and in the adult cerebellum of vertebrates. Found throughout the animal kingdom, ZIC1-5 genes encode five distinct ZIC proteins ...


Lipid Sensing By Mammalian Target Of Rapamycin, Deepak Menon Feb 2017

Lipid Sensing By Mammalian Target Of Rapamycin, Deepak Menon

All Dissertations, Theses, and Capstone Projects

Mammalian target of Rapamycin (mTOR) is a protein kinase that integrates nutrient and growth factor signals to promote cellular growth and proliferation. mTOR exists in two complexes - mTORC1 and mTORC2 that are distinguished by their binding partners and signaling inputs. mTORC1 is responsive to growth factors, amino acids and glucose and is associated with Raptor; whereas, mTORC2 is responsive primarily to growth factors and is associated with Rictor. Raptor and Rictor confer substrate specificity to mTORC1 and mTORC2 respectively. Phosphatidic acid (PA), a lipid second messenger and a central metabolite for membrane phospholipid biosynthesis, is required for the stability and ...


Cancer Metabolism: Fueling More Than Just Growth, Namgyu Lee, Dohoon Kim Dec 2016

Cancer Metabolism: Fueling More Than Just Growth, Namgyu Lee, Dohoon Kim

UMass Metabolic Network Publications

The early landmark discoveries in cancer metabolism research have uncovered metabolic processes that support rapid proliferation, such as aerobic glycolysis (Warburg effect), glutaminolysis, and increased nucleotide biosynthesis. However, there are limitations to the effectiveness of specifically targeting the metabolic processes which support rapid proliferation. First, as other normal proliferative tissues also share similar metabolic features, they may also be affected by such treatments. Secondly, targeting proliferative metabolism may only target the highly proliferating "bulk tumor" cells and not the slower-growing, clinically relevant cancer stem cell subpopulations which may be required for an effective cure. An emerging body of research indicates ...


The Brg1 Chromatin Remodeling Enzyme Links Cancer Cell Metabolism And Proliferation, Qiong Wu, Pasil A. Madany, Jason Dobson, Jake M. Schnabl, Soni Sharma, Tara C. Smith, Andre J. Van Wijnen, Janet L. Stein, Jane B. Lian, Gary S. Stein, Rohini Muthuswami, Anthony N. Imbalzano, Jeffrey A. Nickerson May 2016

The Brg1 Chromatin Remodeling Enzyme Links Cancer Cell Metabolism And Proliferation, Qiong Wu, Pasil A. Madany, Jason Dobson, Jake M. Schnabl, Soni Sharma, Tara C. Smith, Andre J. Van Wijnen, Janet L. Stein, Jane B. Lian, Gary S. Stein, Rohini Muthuswami, Anthony N. Imbalzano, Jeffrey A. Nickerson

Open Access Articles

Cancer cells reprogram cellular metabolism to meet the demands of growth. Identification of the regulatory machinery that regulates cancer-specific metabolic changes may open new avenues for anti-cancer therapeutics. The epigenetic regulator BRG1 is a catalytic ATPase for some mammalian SWI/SNF chromatin remodeling enzymes. BRG1 is a well-characterized tumor suppressor in some human cancers, but is frequently overexpressed without mutation in other cancers, including breast cancer. Here we demonstrate that BRG1 upregulates de novo lipogenesis and that this is crucial for cancer cell proliferation. Knockdown of BRG1 attenuates lipid synthesis by impairing the transcription of enzymes catalyzing fatty acid and ...


Normal Glycolytic Enzyme Activity Is Critical For Hypoxia Inducible Factor-1a Activity And Provides Novel Targets For Inhibiting Tumor Growth, Geoffrey Grandjean Phd Dec 2015

Normal Glycolytic Enzyme Activity Is Critical For Hypoxia Inducible Factor-1a Activity And Provides Novel Targets For Inhibiting Tumor Growth, Geoffrey Grandjean Phd

UT GSBS Dissertations and Theses (Open Access)

Normal Glycolytic Enzyme Activity is Critical for Hypoxia Inducible Factor-1α Activity and Provides Novel Targets for Inhibiting Tumor Growth

By Geoffrey Grandjean

Advisory Professor: Garth Powis, D. Phil

Unique to proliferating cancer cells is the observation that their increased need for energy is provided by a high rate of glycolysis followed by lactic acid fermentation in a process known as the Warburg Effect, a process many times less efficient than oxidative phosphorylation employed by normal cells to satisfy a similar energy demand [1]. This high rate of glycolysis occurs regardless of the concentration of oxygen in the cell and is ...


Analyzation Of Metabolic Reprogramming In Drug-Resistant Mcf-7 Cells, Derick Han, Ho Leung, Andrew Vo May 2015

Analyzation Of Metabolic Reprogramming In Drug-Resistant Mcf-7 Cells, Derick Han, Ho Leung, Andrew Vo

Student Scholar Symposium Abstracts and Posters

The Warburg effect states that cancer cells mainly receive their energy from anaerobic glycolysis. Thus, mitochondria play a different role in the metabolism of cancer cells as opposed to normal, healthy cells. In chemotherapy, there is always a chance of the cancer regressing. Making drug-resistant cancer cells to analyze their metabolism may change how cancer is treated. This study aimed to create drug-resistant MCF-7 cell lines with doxorubicin in order to determine the metabolic changes that have occurred in the process of becoming resistant to drug treatments.


Diabetes And Obesity Induce Transcriptomic And Metabolomic Changes Enhancing Pancreatic Cancer Aggressiveness, Guermarie Velázquez Torres May 2014

Diabetes And Obesity Induce Transcriptomic And Metabolomic Changes Enhancing Pancreatic Cancer Aggressiveness, Guermarie Velázquez Torres

UT GSBS Dissertations and Theses (Open Access)

Pancreatic cancer is one of the most aggressive types of cancer, with poor prognosis that lacks effective diagnostic markers and therapies. It is expected that in 2014 the incidence and the mortality of pancreatic cancer in the United States will be 46,420 and 39,590 respectively. Diabetes and obesity are modifiable risk factors associated with accelerated pancreatic carcinogenesis and tumor progression, but the biological mechanisms are not completely understood. The purpose of this study is to demonstrate direct evidence for the mechanisms mediating these epidemiologic phenomena. Our hypothesis is that obesity and diabetes mellitus type 2 (DM2) accelerate pancreatic ...


Anti-Insulin Resistance Treatments Suppress Her2+ Breast Cancer Growth Via Altering Metabolism, Ping-Chieh Chou May 2014

Anti-Insulin Resistance Treatments Suppress Her2+ Breast Cancer Growth Via Altering Metabolism, Ping-Chieh Chou

UT GSBS Dissertations and Theses (Open Access)

Epidemiological studies have identified that type 2 diabetes mellitus (DM2) is a significant risk factor for carcinogenesis and cancer death, including breast cancer. Our previous finding in patients showed that anti-insulin resistance treatments are associated with improved HER2+ breast cancer survival of diabetic women. However, there were no transgenic mouse models to study the correlation and explain the detailed mechanism. We generated a mouse model of HER2+ breast cancer with DM2 by crossing leptin receptor point mutation (Lepr db/+) and MMTV-ErbB2 (neu) mice. The MMTV-ErbB2/Lepr db/db mice had a poor survival rate compared with MMTV-ErbB2/Lepr +/+ mice, and ...


A Physical Sciences Network Characterization Of Non-Tumorigenic And Metastatic Cells, Abigail Hielscher, D. Wirtz, Et Al. Jan 2013

A Physical Sciences Network Characterization Of Non-Tumorigenic And Metastatic Cells, Abigail Hielscher, D. Wirtz, Et Al.

PCOM Scholarly Papers

To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences-Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results ...


Interleukin-1Β Mediates Metalloproteinase-Dependent Renal Cell Carcinoma Tumor Cell Invasion Through The Activation Of Ccaat Enhancer Binding Protein Β, Brenda L. Petrella, Matthew P. P. Vincenti May 2012

Interleukin-1Β Mediates Metalloproteinase-Dependent Renal Cell Carcinoma Tumor Cell Invasion Through The Activation Of Ccaat Enhancer Binding Protein Β, Brenda L. Petrella, Matthew P. P. Vincenti

Open Dartmouth: Faculty Open Access Scholarship

Effective treatment of metastatic renal cell carcinoma (RCC) remains a major medical concern, as these tumors are refractory to standard therapies and prognosis is poor. Although molecularly targeted therapies have shown some promise in the treatment of this disease, advanced RCC tumors often develop resistance to these drugs. Dissecting the molecular mechanisms underlying the progression to advanced disease is necessary to design alternative and improved treatment strategies. Tumor-associated macrophages (TAMs) found in aggressive RCC tumors produce a variety of inflammatory cytokines, including interleukin-1 b (IL-1b). Moreover, the presence of TAMs and high serum levels of IL-1b in RCC patients correlate ...


Pv1 Down-Regulation Via Shrna Inhibits The Growth Of Pancreatic Adenocarcinoma Xenografts, Sophie J. Deharvengt, Dan Tse, Olga Sideleva, Caitlin Mcgarry, Jason R. Gunn, Daniel S. Longnecker, Catherine Carriere, Radu V. Stan May 2012

Pv1 Down-Regulation Via Shrna Inhibits The Growth Of Pancreatic Adenocarcinoma Xenografts, Sophie J. Deharvengt, Dan Tse, Olga Sideleva, Caitlin Mcgarry, Jason R. Gunn, Daniel S. Longnecker, Catherine Carriere, Radu V. Stan

Open Dartmouth: Faculty Open Access Scholarship

PV1 is an endothelial-specific protein with structural roles in the formation of diaphragms in endothelial cells of normal vessels. PV1 is also highly expressed on endothelial cells of many solid tumours. On the basis of in vitro data, PV1 is thought to actively participate in angiogenesis. To test whether or not PV1 has a function in tumour angiogenesis and in tumour growth in vivo, we have treated pancreatic tumour-bearing mice by single-dose intratumoural delivery of lentiviruses encoding for two different shRNAs targeting murine PV1. We find that PV1 down-regulation by shRNAs inhibits the growth of established tumours derived from two ...


Cdk1 And Plk1 Mediate A Clasp2 Phospho-Switch That Stabilizes Kinetochore–Microtubule Attachments, Ana R. R. Maia, Zaira Garcia, Lilian Kabeche, Marin Barisic Jan 2012

Cdk1 And Plk1 Mediate A Clasp2 Phospho-Switch That Stabilizes Kinetochore–Microtubule Attachments, Ana R. R. Maia, Zaira Garcia, Lilian Kabeche, Marin Barisic

Open Dartmouth: Faculty Open Access Scholarship

Accurate chromosome segregation during mitosis relies on a dynamic kinetochore (KT)-microtubule (MT) interface that switches from a labile to a stable condition in response to correct MT attachments. This transition is essential to satisfy the spindle-assembly checkpoint (SAC) and couple MT-generated force with chromosome movements, but the underlying regulatory mechanism remains unclear. In this study, we show that during mitosis the MT- and KT-associated protein CLASP2 is progressively and distinctively phosphorylated by Cdk1 and Plk1 kinases, concomitant with the establishment of KT-MT attachments. CLASP2 S1234 was phosphorylated by Cdk1, which primed CLASP2 for association with Plk1. Plk1 recruitment to ...


Variations In Mre11/Rad50/Nbs1 Status And Dna Damage-Induced S-Phase Arrest In The Cell Lines Of The Nci60 Panel, Kristen M. K. Garner, Alan Eastman May 2011

Variations In Mre11/Rad50/Nbs1 Status And Dna Damage-Induced S-Phase Arrest In The Cell Lines Of The Nci60 Panel, Kristen M. K. Garner, Alan Eastman

Open Dartmouth: Faculty Open Access Scholarship

The Mre11/Rad50/Nbs1 (MRN) complex is a regulator of cell cycle checkpoints and DNA repair. Defects in MRN can lead to defective S-phase arrest when cells are damaged. Such defects may elicit sensitivity to selected drugs providing a chemical synthetic lethal interaction that could be used to target therapy to tumors with these defects. The goal of this study was to identify these defects in the NCI60 panel of cell lines and identify compounds that might elicit selective cytotoxicity.


Wnt Pathway Reprogramming During Human Embryonal Carcinoma Differentiation And Potential For Therapeutic Targeting, Grace E. Snow, Allison C. Kasper, Alexander M. Busch, Elisabeth Schwarz, Katherine E. Ewings, Thomas Bee, Michael J. Spinella, Ethan Dmitrovsky, Sarah J. Freemantle Oct 2009

Wnt Pathway Reprogramming During Human Embryonal Carcinoma Differentiation And Potential For Therapeutic Targeting, Grace E. Snow, Allison C. Kasper, Alexander M. Busch, Elisabeth Schwarz, Katherine E. Ewings, Thomas Bee, Michael J. Spinella, Ethan Dmitrovsky, Sarah J. Freemantle

Open Dartmouth: Faculty Open Access Scholarship

Testicular germ cell tumors (TGCTs) are classified as seminonas or non-seminomas of which a major subset is embryonal carcinoma (EC) that can differentiate into diverse tissues. The pluripotent nature of human ECs resembles that of embryonic stem (ES) cells. Many Wnt signalling species are regulated during differentiation of TGCT-derived EC cells. This study comprehensively investigated expression profiles of Wnt signalling components regulated during induced differentiation of EC cells and explored the role of key components in maintaining pluripotency.


Growth Factor–Induced Shedding Of Syndecan-1 Confers Glypican-1 Dependence On Mitogenic Responses Of Cancer Cells, Kan Ding, Martha Lopez-Burks, José A. Sánchez-Duran, Murray Korc, Arthur D. Lander Nov 2005

Growth Factor–Induced Shedding Of Syndecan-1 Confers Glypican-1 Dependence On Mitogenic Responses Of Cancer Cells, Kan Ding, Martha Lopez-Burks, José A. Sánchez-Duran, Murray Korc, Arthur D. Lander

Open Dartmouth: Faculty Open Access Scholarship

The cell surface heparan sulfate proteoglycan (HSPG) glypican-1 is up-regulated by pancreatic and breast cancer cells, and its removal renders such cells insensitive to many growth factors. We sought to explain why the cell surface HSPG syndecan-1, which is also up-regulated by these cells and is a known growth factor coreceptor, does not compensate for glypican-1 loss. We show that the initial responses of these cells to the growth factor FGF2 are not glypican dependent, but they become so over time as FGF2 induces shedding of syndecan-1. Manipulations that retain syndecan-1 on the cell surface make long-term FGF2 responses glypican ...


Ube1l Is A Retinoid Target That Triggers Pml/Rarα Degradation And Apoptosis In Acute Promyelocytic Leukemia, Sutisak Kitareewan, Ian Pitha-Rowe, David Sekula, Christopher H. Lowrey, Michael J. Nemeth, Todd R. Golub, Sarah J. Freemantle, Ethan Dmitrovsky Mar 2002

Ube1l Is A Retinoid Target That Triggers Pml/Rarα Degradation And Apoptosis In Acute Promyelocytic Leukemia, Sutisak Kitareewan, Ian Pitha-Rowe, David Sekula, Christopher H. Lowrey, Michael J. Nemeth, Todd R. Golub, Sarah J. Freemantle, Ethan Dmitrovsky

Open Dartmouth: Faculty Open Access Scholarship

All-trans-retinoic acid (RA) treatment induces remissions in acute promyelocytic leukemia (APL) cases expressing the t(15;17) product, promyelocytic leukemia (PML)/RA receptor α (RARα). Microarray analyses previously revealed induction of UBE1L (ubiquitin-activating enzyme E1-like) after RA treatment of NB4 APL cells. We report here that this occurs within 3 h in RA-sensitive but not RA-resistant APL cells, implicating UBE1L as a direct retinoid target. A 1.3-kb fragment of the UBE1L promoter was capable of mediating transcriptional response to RA in a retinoid receptor-selective manner. PML/RARα, a repressor of RA target genes, abolished this UBE1L promoter ...