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Cancer Biology

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Articles 1 - 30 of 122

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition In Cancer, Monserrat Olea-Flores, Miriam Daniela Zuniga-Eulogio, Miguel Angel Mendoza-Catalan, Hugo Alberto Rodriguez-Ruiz, Eduardo Castaneda-Saucedo, Carlos Ortuno-Pineda, Teresita Padilla-Benavides, Napoleon Navarro-Tito Jun 2019

Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition In Cancer, Monserrat Olea-Flores, Miriam Daniela Zuniga-Eulogio, Miguel Angel Mendoza-Catalan, Hugo Alberto Rodriguez-Ruiz, Eduardo Castaneda-Saucedo, Carlos Ortuno-Pineda, Teresita Padilla-Benavides, Napoleon Navarro-Tito

Open Access Articles

Epithelial-mesenchymal transition (EMT) is a reversible cellular process, characterized by changes in gene expression and activation of proteins, favoring the trans-differentiation of the epithelial phenotype to a mesenchymal phenotype. This process increases cell migration and invasion of tumor cells, progression of the cell cycle, and resistance to apoptosis and chemotherapy, all of which support tumor progression. One of the signaling pathways involved in tumor progression is the MAPK pathway. Within this family, the ERK subfamily of proteins is known for its contributions to EMT. The ERK subfamily is divided into typical (ERK 1/2/5), and atypical (ERK 3/4 ...


Crispr-Sonic: Targeted Somatic Oncogene Knock-In Enables Rapid In Vivo Cancer Modeling, Haiwei Mou, Deniz M. Ozata, Jordan L. Smith, Ankur Sheel, Suet-Yan Kwan, Soren Hough, Alper Kucukural, Zachary Kennedy, Yueying Cao, Wen Xue Apr 2019

Crispr-Sonic: Targeted Somatic Oncogene Knock-In Enables Rapid In Vivo Cancer Modeling, Haiwei Mou, Deniz M. Ozata, Jordan L. Smith, Ankur Sheel, Suet-Yan Kwan, Soren Hough, Alper Kucukural, Zachary Kennedy, Yueying Cao, Wen Xue

RNA Therapeutics Institute Publications

CRISPR/Cas9 has revolutionized cancer mouse models. Although loss-of-function genetics by CRISPR/Cas9 is well-established, generating gain-of-function alleles in somatic cancer models is still challenging because of the low efficiency of gene knock-in. Here we developed CRISPR-based Somatic Oncogene kNock-In for Cancer Modeling (CRISPR-SONIC), a method for rapid in vivo cancer modeling using homology-independent repair to integrate oncogenes at a targeted genomic locus. Using a dual guide RNA strategy, we integrated a plasmid donor in the 3'-UTR of mouse beta-actin, allowing co-expression of reporter genes or oncogenes from the beta-actin promoter. We showed that knock-in of oncogenic Ras and ...


Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan Mar 2019

Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

One of the major goals in large-scale genomic studies is to identify genes with a prognostic impact on time-to-event outcomes which provide insight into the disease's process. With rapid developments in high-throughput genomic technologies in the past two decades, the scientific community is able to monitor the expression levels of tens of thousands of genes and proteins resulting in enormous data sets where the number of genomic features is far greater than the number of subjects. Methods based on univariate Cox regression are often used to select genomic features related to survival outcome; however, the Cox model assumes proportional ...


Supervised Dimension Reduction For Large-Scale "Omics" Data With Censored Survival Outcomes Under Possible Non-Proportional Hazards, Lauren Spirko-Burns, Karthik Devarajan Mar 2019

Supervised Dimension Reduction For Large-Scale "Omics" Data With Censored Survival Outcomes Under Possible Non-Proportional Hazards, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

The past two decades have witnessed significant advances in high-throughput ``omics" technologies such as genomics, proteomics, metabolomics, transcriptomics and radiomics. These technologies have enabled simultaneous measurement of the expression levels of tens of thousands of features from individual patient samples and have generated enormous amounts of data that require analysis and interpretation. One specific area of interest has been in studying the relationship between these features and patient outcomes, such as overall and recurrence-free survival, with the goal of developing a predictive ``omics" profile. Large-scale studies often suffer from the presence of a large fraction of censored observations and potential ...


Colorectal Cancer Liver Metastatic Growth Depends On Pad4-Driven Citrullination Of The Extracellular Matrix, A. E. Yuzhalin, A. N. Gordon-Weeks, M. L. Tognoli, K. Jones, B. Markelc, R. Konietzny, R. Fischer, Aaron Muth, E. O'Neill, Paul R. Thompson, P. J. Venables, B. M. Kessler, S. Y. Lim, R. J. Muschel Nov 2018

Colorectal Cancer Liver Metastatic Growth Depends On Pad4-Driven Citrullination Of The Extracellular Matrix, A. E. Yuzhalin, A. N. Gordon-Weeks, M. L. Tognoli, K. Jones, B. Markelc, R. Konietzny, R. Fischer, Aaron Muth, E. O'Neill, Paul R. Thompson, P. J. Venables, B. M. Kessler, S. Y. Lim, R. J. Muschel

Open Access Articles

Citrullination of proteins, a post-translational conversion of arginine residues to citrulline, is recognized in rheumatoid arthritis, but largely undocumented in cancer. Here we show that citrullination of the extracellular matrix by cancer cell derived peptidylarginine deiminase 4 (PAD4) is essential for the growth of liver metastases from colorectal cancer (CRC). Using proteomics, we demonstrate that liver metastases exhibit higher levels of citrullination and PAD4 than unaffected liver, primary CRC or adjacent colonic mucosa. Functional significance for citrullination in metastatic growth is evident in murine models where inhibition of citrullination substantially reduces liver metastatic burden. Additionally, citrullination of a key matrix ...


Signaling Pathways Induced By Leptin During Epithelial(-)Mesenchymal Transition In Breast Cancer, Monserrat Olea-Flores, Juan Carlos Juarez-Cruz, Miguel A. Mendoza-Catalan, Teresita Padilla-Benavides, Napoleon Navarro-Tito Nov 2018

Signaling Pathways Induced By Leptin During Epithelial(-)Mesenchymal Transition In Breast Cancer, Monserrat Olea-Flores, Juan Carlos Juarez-Cruz, Miguel A. Mendoza-Catalan, Teresita Padilla-Benavides, Napoleon Navarro-Tito

Open Access Articles

Leptin is an adipokine that is overexpressed in obese and overweight people. Interestingly, women with breast cancer present high levels of leptin and of its receptor ObR. Leptin plays an important role in breast cancer progression due to the biological processes it participates in, such as epithelial(-)mesenchymal transition (EMT). EMT consists of a series of orchestrated events in which cell(-)cell and cell(-)extracellular matrix interactions are altered and lead to the release of epithelial cells from the surrounding tissue. The cytoskeleton is also re-arranged, allowing the three-dimensional movement of epithelial cells into the extracellular matrix. This transition provides ...


Synthesis And Biological Evaluation Of Phaeosphaeride A Derivatives As Antitumor Agents, Victoria Abzianidze, Petr Beltyukov, Sofya Zakharenkova, Natalia Moiseeva, Jennifer Mejia, Alvin Holder, Yuri Trishin, Alexander Berestetskiy, Victor Kuznetsov Nov 2018

Synthesis And Biological Evaluation Of Phaeosphaeride A Derivatives As Antitumor Agents, Victoria Abzianidze, Petr Beltyukov, Sofya Zakharenkova, Natalia Moiseeva, Jennifer Mejia, Alvin Holder, Yuri Trishin, Alexander Berestetskiy, Victor Kuznetsov

Chemistry & Biochemistry Faculty Publications

New derivatives of phaeosphaeride A (PPA) were synthesized and characterized. Anti-tumor activity studies were carried out on the HCT-116, PC3, MCF-7, A549, К562, NCI-Н929, Jurkat, THP-1, RPMI8228 tumor cell lines, and on the HEF cell line. All of the compounds synthesized were found to have better efficacy than PPA towards the tumor cell lines mentioned. Compound 6 was potent against six cancer cell lines, HCT-116, PC-3, K562, NCI-H929, Jurkat, and RPMI8226, showing a 47, 13.5, 16, 4, 1.5, and 7-fold increase in anticancer activity comparative to those of etoposide, respectively. Compound 1 possessed selectivity toward the NCI-H929 cell ...


Rare Gene Fusion Rearrangement Sptnb1-Pdgfrb In An Atypical Myeloproliferative Neoplasm, Vanessa Fiorini Furtado, Neeraj Y. Saini, William V. Walsh, Venu G. Bathini, Patricia M. Miron Oct 2018

Rare Gene Fusion Rearrangement Sptnb1-Pdgfrb In An Atypical Myeloproliferative Neoplasm, Vanessa Fiorini Furtado, Neeraj Y. Saini, William V. Walsh, Venu G. Bathini, Patricia M. Miron

Open Access Articles

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia recognizes a distinct class of myeloid and lymphoid tumors with eosinophilia-related proliferations associated with specific gene rearrangements, one of which involves rearrangements of platelet-derived growth factor receptor B (PDGFRB) gene. We report a case of a rare PDGFRB rearrangement with SPTNB1 (spectrin beta, nonerythrocytic 1) that presented as atypical myeloproliferative neoplasm.


8th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association Oct 2018

8th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

MD Anderson Cancer Center Postdoctoral Association Annual Postdoctoral Science Symposium Abstracts

The mission of the Annual Postdoctoral Science Symposium (APSS) is to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience. The MD Anderson Postdoctoral Association convened its inaugural Annual Postdoctoral Science Symposium (APSS) on August 4, 2011.

The APSS provides a professional venue for postdoctoral scientists to develop, clarify, and refine their research as a result of formal reviews and critiques of faculty and other postdoctoral scientists. Additionally, attendees discuss current research on a broad range of subjects while promoting academic interactions and enrichment and developing new collaborations.


Tumor-Stroma Interactions Differentially Alter Drug Sensitivity Based On The Origin Of Stromal Cells, Benjamin D. Landry, Thomas Leete, Ryan Richards, Peter Cruz-Gordillo, Hannah R. Schwartz, Megan E. Honeywell, Gary Ren, Alyssa D. Schwartz, Shelly R. Peyton, Michael J. Lee Aug 2018

Tumor-Stroma Interactions Differentially Alter Drug Sensitivity Based On The Origin Of Stromal Cells, Benjamin D. Landry, Thomas Leete, Ryan Richards, Peter Cruz-Gordillo, Hannah R. Schwartz, Megan E. Honeywell, Gary Ren, Alyssa D. Schwartz, Shelly R. Peyton, Michael J. Lee

Program in Systems Biology Publications and Presentations

Due to tumor heterogeneity, most believe that effective treatments should be tailored to the features of an individual tumor or tumor subclass. It is still unclear, however, what information should be considered for optimal disease stratification, and most prior work focuses on tumor genomics. Here, we focus on the tumor microenvironment. Using a large-scale coculture assay optimized to measure drug-induced cell death, we identify tumor-stroma interactions that modulate drug sensitivity. Our data show that the chemo-insensitivity typically associated with aggressive subtypes of breast cancer is not observed if these cells are grown in 2D or 3D monoculture, but is manifested ...


Llc Tumor Cells-Derivated Factors Reduces Adipogenesis In Co-Culture System, Magno Alves Lopes, Felipe Oliveira Franco, Felipe Henriques, Sidney Barnabe Peres, Miguel Luiz Batista Jr. Jul 2018

Llc Tumor Cells-Derivated Factors Reduces Adipogenesis In Co-Culture System, Magno Alves Lopes, Felipe Oliveira Franco, Felipe Henriques, Sidney Barnabe Peres, Miguel Luiz Batista Jr.

Open Access Articles

Cancer cachexia (CC) is a multifactorial syndrome with an unknown etiology. The primary symptom is the progressive reduction of the body weight. Recently, down-regulation of adipogenic and lipogenic genes were demonstrated to be early affected during cachexia progression in adipose tissue (AT), resulting in AT remodeling. Thus, this study aimed to evaluate in a co-culture system the influence of the Lewis Lung Carcinoma (LLC) tumor cells (c/c-LLC) in an established pre-adipocyte cell line 3T3-L1 adipogenic capacity. c/c-LLC in the presence of 3T3-L1 caused a reduction in lipids accumulation, suggesting that secretory tumor cells products may affect adipogenesis. Interestingly ...


Etv4 Transcription Factor And Mmp13 Metalloprotease Are Interplaying Actors Of Breast Tumorigenesis, Mandy Dumortier, Franck Ladam, Isabelle Damour, Sophie Vacher, Ivan Bieche, Nathalie Marchand, Yvan De Launoit, David Tulasne, Anne Chotteau-Lelievre Jul 2018

Etv4 Transcription Factor And Mmp13 Metalloprotease Are Interplaying Actors Of Breast Tumorigenesis, Mandy Dumortier, Franck Ladam, Isabelle Damour, Sophie Vacher, Ivan Bieche, Nathalie Marchand, Yvan De Launoit, David Tulasne, Anne Chotteau-Lelievre

Open Access Articles

BACKGROUND: The ETS transcription factor ETV4 is involved in the main steps of organogenesis and is also a significant mediator of tumorigenesis and metastasis, such as in breast cancer. Indeed, ETV4 is overexpressed in breast tumors and is associated with distant metastasis and poor prognosis. However, the cellular and molecular events regulated by this factor are still misunderstood. In mammary epithelial cells, ETV4 controls the expression of many genes, MMP13 among them. The aim of this study was to understand the function of MMP13 during ETV4-driven tumorigenesis.

METHODS: Different constructs of the MMP13 gene promoter were used to study the ...


Identification Of A Novel Invasion-Promoting Region In Insulin Receptor Substrate 2, Jose Mercado-Matos, Jenny Janusis, Sha Zhu, Samuel S. Chen, Leslie M. Shaw Jun 2018

Identification Of A Novel Invasion-Promoting Region In Insulin Receptor Substrate 2, Jose Mercado-Matos, Jenny Janusis, Sha Zhu, Samuel S. Chen, Leslie M. Shaw

University of Massachusetts Medical School Faculty Publications

Although the insulin receptor substrate (IRS) proteins IRS1 and IRS2 share considerable homology and activate common signaling pathways, their contributions to breast cancer are distinct. IRS1 has been implicated in the proliferation and survival of breast tumor cells. In contrast, IRS2 facilitates glycolysis, invasion, and metastasis. To determine the mechanistic basis for IRS2-dependent functions, we investigated unique structural features of IRS2 that are required for invasion. Our studies revealed that the ability of IRS2 to promote invasion is dependent upon upstream insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor (IR) activation and the recruitment and activation of phosphatidylinositol 3-kinase (PI3K ...


Cell Clustering Mediated By The Adhesion Protein Pvrl4 Is Necessary For Alpha6beta4 Integrin-Promoted Ferroptosis Resistance In Matrix-Detached Cells, Caitlin W. Brown, John J. Amante, Arthur M. Mercurio Jun 2018

Cell Clustering Mediated By The Adhesion Protein Pvrl4 Is Necessary For Alpha6beta4 Integrin-Promoted Ferroptosis Resistance In Matrix-Detached Cells, Caitlin W. Brown, John J. Amante, Arthur M. Mercurio

University of Massachusetts Medical School Faculty Publications

Ferroptosis is an iron-dependent form of programmed cell death characterized by the accumulation of lipid-targeting reactive oxygen species that kill cells by damaging their plasma membrane. The lipid-repair enzyme glutathione peroxidase 4 (GPX4) protects against this oxidative damage and enables cells to resist ferroptosis. Recent work has revealed that matrix-detached carcinoma cells can be susceptible to ferroptosis and that they can evade this fate through the signaling properties of the alpha6beta4 integrin, which sustains GPX4 expression. Although these findings on ferroptosis are provocative, they differ from those in previous studies indicating that matrix-detached cells are prone to apoptosis, via a ...


Dynamics Of Human Protein Kinase Aurora A Linked To Drug Selectivity, Warintra Pitsawong, Vanessa Buosi, Renee Otten, Roman V. Agafonov, Adelajda Zorba, Nadja Kern, Steffen Kutter, Gunther Kern, Ricardo Ap Padua, Xavier Meniche, Dorothee Kern Jun 2018

Dynamics Of Human Protein Kinase Aurora A Linked To Drug Selectivity, Warintra Pitsawong, Vanessa Buosi, Renee Otten, Roman V. Agafonov, Adelajda Zorba, Nadja Kern, Steffen Kutter, Gunther Kern, Ricardo Ap Padua, Xavier Meniche, Dorothee Kern

Open Access Articles

Protein kinases are major drug targets, but the development of highly-selective inhibitors has been challenging due to the similarity of their active sites. The observation of distinct structural states of the fully-conserved Asp-Phe-Gly (DFG) loop has put the concept of conformational selection for the DFG-state at the center of kinase drug discovery. Recently, it was shown that Gleevec selectivity for the Tyr-kinase Abl was instead rooted in conformational changes after drug binding. Here, we investigate whether protein dynamics after binding is a more general paradigm for drug selectivity by characterizing the binding of several approved drugs to the Ser/Thr-kinase ...


Cip2a Facilitates The G1/S Cell Cycle Transition Via B-Myb In Human Papillomavirus 16 Oncoprotein E6-Expressing Cells, Yonghao Tian, Hanxiang Chen, Lijun Qiao, Wenhao Zhang, Jingyi Zheng, Weiming Zhao, Jason J. Chen, Weifang Zhang Jun 2018

Cip2a Facilitates The G1/S Cell Cycle Transition Via B-Myb In Human Papillomavirus 16 Oncoprotein E6-Expressing Cells, Yonghao Tian, Hanxiang Chen, Lijun Qiao, Wenhao Zhang, Jingyi Zheng, Weiming Zhao, Jason J. Chen, Weifang Zhang

Open Access Articles

Infection with high-risk human papillomaviruses (HR-HPVs, including HPV-16, HPV-18, HPV-31) plays a central aetiologic role in the development of cervical carcinoma. The transforming properties of HR-HPVs mainly reside in viral oncoproteins E6 and E7. E6 protein degrades the tumour suppressor p53 and abrogates cell cycle checkpoints. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that is involved in the carcinogenesis of many human malignancies. Our previous data showed that CIP2A was overexpressed in cervical cancer. However, the regulation of CIP2A by HPV-16E6 remains to be elucidated. In this study, we demonstrated that HPV-16E6 significantly up-regulated CIP2A mRNA and ...


Imp3 Stabilization Of Wnt5b Mrna Facilitates Taz Activation In Breast Cancer, Sanjoy Samanta, Santosh Guru, Ameer L. Elaimy, John J. Amante, Jianhong Ou, Jun Yu, Lihua Julie Zhu, Arthur M. Mercurio May 2018

Imp3 Stabilization Of Wnt5b Mrna Facilitates Taz Activation In Breast Cancer, Sanjoy Samanta, Santosh Guru, Ameer L. Elaimy, John J. Amante, Jianhong Ou, Jun Yu, Lihua Julie Zhu, Arthur M. Mercurio

Open Access Articles

Insulin-like growth factor-2 mRNA-binding protein 3 (IMP3) is an oncofetal protein associated with many aggressive cancers and implicated in the function of breast cancer stem cells (CSCs). The mechanisms involved, however, are poorly understood. We observed that IMP3 facilitates the activation of TAZ, a transcriptional co-activator of Hippo signaling that is necessary for the function of breast CSCs. The mechanism by which IMP3 activates TAZ involves both mRNA stability and transcriptional regulation. IMP3 stabilizes the mRNA of an alternative WNT ligand (WNT5B) indirectly by repressing miR145-5p, which targets WNT5B, resulting in TAZ activation by alternative WNT signaling. IMP3 also facilitates ...


Genetic Testing And A Real World Case Of Lynch Syndrome, Paige Montanaro May 2018

Genetic Testing And A Real World Case Of Lynch Syndrome, Paige Montanaro

Senior Honors Projects

In recent years, advancements in genetic testing methods have revolutionized the medical field by enhancing the ability to identify persons with an inherited predisposition to cancer. According to the American Society for Clinical Oncology, individuals should undergo genetic testing when he or she meets the following criteria: the individual demonstrates familial history that indicates a predisposition to certain cancers, the test can be adequately interpreted, and the results will aid in the diagnosis, treatment, or management of the patient or additional family members at risk. Genetic testing can be done on samples of hair, skin, blood, amniotic fluid, or other ...


Cold Atmospheric Plasma Induces Atp-Dependent Endocytosis Of Nanoparticles And Synergistic U373mg Cancer Cell Death, Zhonglei He, Kangze Liu, Eline Manaloto, Alan Casey, George P. Cribaro, Hugh Byrne, Furong Tian, Carlos Barcia, Gillian E. Conway, Patrick Cullen, James Curtin Mar 2018

Cold Atmospheric Plasma Induces Atp-Dependent Endocytosis Of Nanoparticles And Synergistic U373mg Cancer Cell Death, Zhonglei He, Kangze Liu, Eline Manaloto, Alan Casey, George P. Cribaro, Hugh Byrne, Furong Tian, Carlos Barcia, Gillian E. Conway, Patrick Cullen, James Curtin

Articles

Gold nanoparticles (AuNP) have potential as both diagnostic and therapeutic vehicles. However, selective targeting and uptake in cancer cells remains challenging. Cold atmospheric plasma (CAP) can be combined with AuNP to achieve synergistic anti-cancer cytotoxicity. To explore synergistic mechanisms, we demonstrate both rate of AuNP uptake and total amount accumulated in U373MG Glioblastoma multiforme (GBM) cells are signifcantly increased when exposed to 75kV CAP generated by dielectric barrier discharge. No signifcant changes in the physical parameters of AuNP were caused by CAP but active transport mechanisms were stimulated in cells. Unlike many other biological efects of CAP, long-lived reactive species ...


Profiling Prostate Cancer Therapeutic Resistance, Cameron A. Wade, Natasha Kyprianou Mar 2018

Profiling Prostate Cancer Therapeutic Resistance, Cameron A. Wade, Natasha Kyprianou

Urology Faculty Publications

The major challenge in the treatment of patients with advanced lethal prostate cancer is therapeutic resistance to androgen-deprivation therapy (ADT) and chemotherapy. Overriding this resistance requires understanding of the driving mechanisms of the tumor microenvironment, not just the androgen receptor (AR)-signaling cascade, that facilitate therapeutic resistance in order to identify new drug targets. The tumor microenvironment enables key signaling pathways promoting cancer cell survival and invasion via resistance to anoikis. In particular, the process of epithelial-mesenchymal-transition (EMT), directed by transforming growth factor-β (TGF-β), confers stem cell properties and acquisition of a migratory and invasive phenotype via resistance to anoikis ...


Inactivation Of Myeloma Cancer Cells By Helium And Argon Plasma Jets: The Effect Comparison And The Key Reactive Species, Zeyu Chen, Qingjie Cui, Chen Chen, Dehui Xu, Dingxin Liu, H. L. Chen, Michael G. Kong Feb 2018

Inactivation Of Myeloma Cancer Cells By Helium And Argon Plasma Jets: The Effect Comparison And The Key Reactive Species, Zeyu Chen, Qingjie Cui, Chen Chen, Dehui Xu, Dingxin Liu, H. L. Chen, Michael G. Kong

Bioelectrics Publications

In plasma cancer therapy, the inactivation of cancer cells under plasma treatment is closely related to the reactive oxygen and nitrogen species (RONS) induced by plasmas. Quantitative study on the plasma-induced RONS that related to cancer cells apoptosis is critical for advancing the research of plasma cancer therapy. In this paper, the effects of several reactive species on the inactivation of LP-1 myeloma cancer cells are comparatively studied with variable working gas composition, surrounding gas composition, and discharge power. The results show that helium plasma jet has a higher cell inactivation efficiency than argon plasma jet under the same discharge ...


Cold Atmospheric Plasma As A Potential Tool For Multiple Myeloma Treatment, Dehui Xu, Yujing Xu, Qingjie Cui, Dingxin Liu, Zhijie Liu, Xiaohua Wang, Yanjie Yang, Niaojuan Feng, Rong Liang, Hailan Chen, Kai Ye, Michael G. Kong Jan 2018

Cold Atmospheric Plasma As A Potential Tool For Multiple Myeloma Treatment, Dehui Xu, Yujing Xu, Qingjie Cui, Dingxin Liu, Zhijie Liu, Xiaohua Wang, Yanjie Yang, Niaojuan Feng, Rong Liang, Hailan Chen, Kai Ye, Michael G. Kong

Bioelectrics Publications

Multiple myeloma (MM) is a fatal and incurable hematological malignancy thus new therapy need to be developed. Cold atmospheric plasma, a new technology that could generate various active species, could efficiently induce various tumor cells apoptosis. More details about the interaction of plasma and tumor cells need to be addressed before the application of gas plasma in clinical cancer treatment. In this study, we demonstrate that He+O2 plasma could efficiently induce myeloma cell apoptosis through the activation of CD95 and downstream caspase cascades. Extracellular and intracellular reactive oxygen species (ROS) accumulation is essential for CD95-mediated cell apoptosis in ...


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 ...


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 ...


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 ...


Tox Regulates Growth, Dna Repair, And Genomic Instability In T-Cell Acute Lymphoblastic Leukemia, Riadh Lobbardi, Jordan Pinder, Barbara Martinez-Pastor, Marina Theodorou, Jessica S. Blackburn, Brian J. Abraham, Yuka Namiki, Marc Mansour, Nouran S. Abdelfattah, Aleksey Molodtsov, Gabriela Alexe, Debra Toiber, Manon De Waard, Esha Jain, Myriam Boukhali, Mattia Lion, Deepak Bhere, Khalid Shah, Alejandro Gutierrez, Kimberly Stegmaier, Lewis B. Silverman, Ruslan I. Sadreyev, John M. Asara, Marjorie A. Oettinger, Wilhelm Haas, A. Thomas Look, Richard A. Young, Raul Mostoslavsky, Graham Dellaire, David M. Langenau Nov 2017

Tox Regulates Growth, Dna Repair, And Genomic Instability In T-Cell Acute Lymphoblastic Leukemia, Riadh Lobbardi, Jordan Pinder, Barbara Martinez-Pastor, Marina Theodorou, Jessica S. Blackburn, Brian J. Abraham, Yuka Namiki, Marc Mansour, Nouran S. Abdelfattah, Aleksey Molodtsov, Gabriela Alexe, Debra Toiber, Manon De Waard, Esha Jain, Myriam Boukhali, Mattia Lion, Deepak Bhere, Khalid Shah, Alejandro Gutierrez, Kimberly Stegmaier, Lewis B. Silverman, Ruslan I. Sadreyev, John M. Asara, Marjorie A. Oettinger, Wilhelm Haas, A. Thomas Look, Richard A. Young, Raul Mostoslavsky, Graham Dellaire, David M. Langenau

Molecular and Cellular Biochemistry Faculty Publications

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes. Using a transgenic screen in zebrafish, thymocyte selection–associated high mobility group box protein (TOX) was uncovered as a collaborating oncogenic driver that accelerated T-ALL onset by expanding the initiating pool of transformed clones and elevating genomic instability. TOX is highly expressed in a majority of human T-ALL and is required for proliferation and continued xenograft growth in mice. Using a wide array of functional analyses, we uncovered that TOX binds directly to KU70/80 and suppresses recruitment of this complex to DNA breaks to inhibit nonhomologous end joining ...


Nanoparticle Delivery Of Mir-34a Eradicates Long-Term-Cultured Breast Cancer Stem Cells Via Targeting C22orf28 Directly, Xiaoti Lin, Weiyu Chen, Fengqin Wei, Binhua P. Zhou, Mien-Chie Hung, Xiaoming Xie Oct 2017

Nanoparticle Delivery Of Mir-34a Eradicates Long-Term-Cultured Breast Cancer Stem Cells Via Targeting C22orf28 Directly, Xiaoti Lin, Weiyu Chen, Fengqin Wei, Binhua P. Zhou, Mien-Chie Hung, Xiaoming Xie

Molecular and Cellular Biochemistry Faculty Publications

Rationale: Cancer stem cells (CSCs) have been implicated as the seeds of therapeutic resistance and metastasis, due to their unique abilities of self-renew, wide differentiation potentials and resistance to most conventional therapies. It is a proactive strategy for cancer therapy to eradicate CSCs. Methods: Tumor tissue-derived breast CSCs (BCSC), including XM322 and XM607, were isolated by fluorescence-activated cell sorting (FACS); while cell line-derived BCSC, including MDA-MB-231.SC and MCF-7.SC, were purified by magnetic-activated cell sorting (MACS). Analyses of microRNA and mRNA expression array profiles were performed in multiple breast cell lines. The mentioned nanoparticles were constructed following the standard ...


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 ...


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 ...


Stabilization Of The Transcription Factors Slug And Twist By The Deubiquitinase Dub3 Is A Key Requirement For Tumor Metastasis, Yiwei Lin, Yu Wang, Qing Shi, Qian Yu, Cuicui Liu, Jing Feng, Jiong Deng, B. Mark Evers, Binhua P. Zhou, Yadi Wu Aug 2017

Stabilization Of The Transcription Factors Slug And Twist By The Deubiquitinase Dub3 Is A Key Requirement For Tumor Metastasis, Yiwei Lin, Yu Wang, Qing Shi, Qian Yu, Cuicui Liu, Jing Feng, Jiong Deng, B. Mark Evers, Binhua P. Zhou, Yadi Wu

Molecular and Cellular Biochemistry Faculty Publications

The Epithelial-mesenchymal transition (EMT) represents a cellular de-differentiation process that provides cells with the increased plasticity required during embryonic development, tissue remodeling, wound healing and metastasis. Slug and Twist are two key EMT transcription factors (EMT-TFs) that are tightly regulated via ubiquitination and degradation. How Slug and Twist escape degradation and become stabilized in cancer cells remains unclear. One plausible mechanism of Slug and Twist stabilization involves removal of ubiquitin by deubiquitinases (DUBs). In this study, we identified Dub3 as a novel DUB for both Slug and Twist. We further found that Dub3 overexpression increased Slug and Twist protein levels ...