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University of Massachusetts Medical School Faculty Publications

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Articles 1 - 21 of 21

Full-Text Articles in Cancer Biology

Leptin Promotes Expression Of Emt-Related Transcription Factors And Invasion In A Src And Fak-Dependent Pathway In Mcf10a Mammary Epithelial Cells, Monserrat Olea-Flores, Miriam Zuñiga-Eulogio, Arvey Tacuba-Saavedra, Magdalena Bueno-Salgado, Andrea Sánchez-Carvajal, Yovani Vargas-Santiago, Miguel A. Mendoza-Catalán, Eduardo Pérez Salazar, Alejandra García-Hernández, Teresita Padilla-Benavides, Napoleón Navarro-Tito Aug 2019

Leptin Promotes Expression Of Emt-Related Transcription Factors And Invasion In A Src And Fak-Dependent Pathway In Mcf10a Mammary Epithelial Cells, Monserrat Olea-Flores, Miriam Zuñiga-Eulogio, Arvey Tacuba-Saavedra, Magdalena Bueno-Salgado, Andrea Sánchez-Carvajal, Yovani Vargas-Santiago, Miguel A. Mendoza-Catalán, Eduardo Pérez Salazar, Alejandra García-Hernández, Teresita Padilla-Benavides, Napoleón Navarro-Tito

University of Massachusetts Medical School Faculty Publications

Leptin is one of the main adipokines secreted in breast tissue, and has been associated with epithelial-mesenchymal transition (EMT) and tumor progression in breast cancer. Leptin promotes EMT, cell migration and invasion in epithelial breast cells, leading to tumor progression. However, the molecular mechanism that underlies these events is not fully understood; however, the activation of different signaling pathways appears to be essential. In this sense, the effect of leptin on the activation of kinases like Src and FAK, which regulate signaling pathways that activate the EMT program, has not been completely described. Therefore, we investigated the involvement of these ...


Tumor Cell-Organized Fibronectin Is Required To Maintain A Dormant Breast Cancer Population, Lauren E. Barney, Christopher L. Hall, Alyssa D. Schwartz, Akia N. Parks, Christopher Sparages, Sualyneth Galarza, Manu O. Platt, Arthur M. Mercurio, Shelly R. Peyton Jul 2019

Tumor Cell-Organized Fibronectin Is Required To Maintain A Dormant Breast Cancer Population, Lauren E. Barney, Christopher L. Hall, Alyssa D. Schwartz, Akia N. Parks, Christopher Sparages, Sualyneth Galarza, Manu O. Platt, Arthur M. Mercurio, Shelly R. Peyton

University of Massachusetts Medical School Faculty Publications

Tumors can undergo long periods of dormancy, with cancer cells entering a largely quiescent, non-proliferative state before reactivation and outgrowth. For a patient, these post-remission tumors are often drug resistant and highly aggressive, resulting in poor prognosis. To understand the role of the extracellular matrix (ECM) in regulating tumor dormancy, we created an in vitro cell culture system that combines carefully controlled ECM substrates with nutrient deprivation to observe entrance into and exit from dormancy with live imaging. We saw that cell populations capable of surviving entrance into long-term dormancy were heterogeneous, containing quiescent, cell cycle arrested, and actively proliferating ...


Pathognomonic And Epistatic Genetic Alterations In B-Cell Non-Hodgkin Lymphoma, Man Chun John Ma, Benjamin J. Chen, Michael R. Green Jun 2019

Pathognomonic And Epistatic Genetic Alterations In B-Cell Non-Hodgkin Lymphoma, Man Chun John Ma, Benjamin J. Chen, Michael R. Green

University of Massachusetts Medical School Faculty Publications

B-cell non-Hodgkin lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL such as diffuse large B-cell lymphoma (DLBCL) have been comprehensively interrogated at the genomic level, but other less common subtypes such as mantle cell lymphoma (MCL) remain sparsely characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared to identify conserved or subtype-specific patterns of genomic alterations. Here, we employed a large targeted hybrid-capture sequencing approach encompassing 380 genes to interrogate the genomic landscapes of 755 B-NHL tumors at high depth; primarily including DLBCL, MCL, follicular lymphoma ...


Brg1 Is A Prognostic Indicator And A Potential Therapeutic Target For Prostate Cancer, Rohini Muthuswami, Leeann Bailey, Radhakrishnan Rakesh, Anthony N. Imbalzano, Jeffrey A. Nickerson, Joel W. Hockensmith Jan 2019

Brg1 Is A Prognostic Indicator And A Potential Therapeutic Target For Prostate Cancer, Rohini Muthuswami, Leeann Bailey, Radhakrishnan Rakesh, Anthony N. Imbalzano, Jeffrey A. Nickerson, Joel W. Hockensmith

University of Massachusetts Medical School Faculty Publications

Brahma-related gene 1 (BRG1) is one of two mutually exclusive ATPases that function as the catalytic subunit of human SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling enzymes. BRG1 has been identified as a tumor suppressor in some cancer types but has been shown to be expressed at elevated levels, relative to normal tissue, in other cancers. Using TCGA (The Cancer Genome Atlas) prostate cancer database, we determined that BRG1 mRNA and protein expression is elevated in prostate tumors relative to normal prostate tissue. Only 3 of 491 (0.6%) sequenced tumors showed amplification of the locus or mutation in 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 ...


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

University of Massachusetts Medical School Faculty Publications

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 ...


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 ...


Novel Magnetic Resonance Imaging Strategy Targeting Neurotensin Receptors In Detection Of Prostate Cancer, Mitul M. Desai, Neville Tam, Robert E. Carraway, Shuk-Mei Ho, Craig F. Ferris, Jean A. King Aug 2017

Novel Magnetic Resonance Imaging Strategy Targeting Neurotensin Receptors In Detection Of Prostate Cancer, Mitul M. Desai, Neville Tam, Robert E. Carraway, Shuk-Mei Ho, Craig F. Ferris, Jean A. King

University of Massachusetts Medical School Faculty Publications

Prostate cancer is the second leading cause of all male cancer deaths. One of the factors present in malignant prostate cells and shown to support its metastatic growth is the neuropeptide neurotensin (NT). The primary goal of the present study was to establish the feasibility of using a newly developed paramagnetic receptor ligand for NT and non-invasive ultrahigh-field magnetic resonance (MR) imaging to visualize prostate cancer in rodents. Orthotropic xenografts were initiated in six-week old male BALB/c nu/nu athymic mice (n = 28) by intra-prostatic (ventral lobe) inoculation of human prostate cancer cells (10 μL of PC3 cells (10 ...


Human And Epstein-Barr Virus Mirna Profiling As Predictive Biomarkers For Endemic Burkitt Lymphoma, Cliff I. Oduor, Mercedeh Movassagh, Yasin Kaymaz, Kiprotich Chelimo, Juliana A. Otieno, John M. Ong'echa, Ann M. Moormann, Jeffrey A. Bailey Mar 2017

Human And Epstein-Barr Virus Mirna Profiling As Predictive Biomarkers For Endemic Burkitt Lymphoma, Cliff I. Oduor, Mercedeh Movassagh, Yasin Kaymaz, Kiprotich Chelimo, Juliana A. Otieno, John M. Ong'echa, Ann M. Moormann, Jeffrey A. Bailey

University of Massachusetts Medical School Faculty Publications

Endemic Burkitt lymphoma (eBL) is an aggressive B cell lymphoma and is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum malaria co-infections. Central to BL oncogenesis is the over-expression of the MYC proto-oncogene which is caused by a translocation of an Ig enhancer in approximation to the myc gene. While whole genome/transcriptome sequencing methods have been used to define driver mutations and transcriptional dysregulation, microRNA (miRNA) dysregulation and differential expression has yet to be fully characterized. We hypothesized that both human and EBV miRNAs contribute to eBL clinical presentation, disease progression, and poor outcomes. Using sensitive and precise deep ...


Crosstalk Between Brca-Fanconi Anemia And Mismatch Repair Pathways Prevents Msh2-Dependent Aberrant Dna Damage Responses, Min Peng, Jenny X. Xie, Anna J. Ucher, Janet Stavnezer, Sharon B. Cantor Aug 2014

Crosstalk Between Brca-Fanconi Anemia And Mismatch Repair Pathways Prevents Msh2-Dependent Aberrant Dna Damage Responses, Min Peng, Jenny X. Xie, Anna J. Ucher, Janet Stavnezer, Sharon B. Cantor

University of Massachusetts Medical School Faculty Publications

Several proteins in the BRCA-Fanconi anemia (FA) pathway, such as FANCJ, BRCA1, and FANCD2, interact with mismatch repair (MMR) pathway factors, but the significance of this link remains unknown. Unlike the BRCA-FA pathway, the MMR pathway is not essential for cells to survive toxic DNA interstrand crosslinks (ICLs), although MMR proteins bind ICLs and other DNA structures that form at stalled replication forks. We hypothesized that MMR proteins corrupt ICL repair in cells that lack crosstalk between BRCA-FA and MMR pathways. Here, we show that ICL sensitivity of cells lacking the interaction between FANCJ and the MMR protein MLH1 is ...


Dicer Cooperates With P53 To Suppress Dna Damage And Skin Carcinogenesis In Mice, Stephen Lyle, Kathleen Hoover, Cansu Colpan, Zhiqing Zhu, Zdenka Matijasevic, Stephen N. Jones Jun 2014

Dicer Cooperates With P53 To Suppress Dna Damage And Skin Carcinogenesis In Mice, Stephen Lyle, Kathleen Hoover, Cansu Colpan, Zhiqing Zhu, Zdenka Matijasevic, Stephen N. Jones

University of Massachusetts Medical School Faculty Publications

Dicer is required for the maturation of microRNA, and loss of Dicer and miRNA processing has been found to alter numerous biological events during embryogenesis, including the development of mammalian skin and hair. We have previously examined the role of miRNA biogenesis in mouse embryonic fibroblasts and found that deletion of Dicer induces cell senescence regulated, in part, by the p53 tumor suppressor. Although Dicer and miRNA molecules are thought to have either oncogenic or tumor suppressing roles in various types of cancer, a role for Dicer and miRNAs in skin carcinogenesis has not been established. Here we show that ...


Genetic Models Of Apoptosis-Induced Proliferation Decipher Activation Of Jnk And Identify A Requirement Of Egfr Signaling For Tissue Regenerative Responses In Drosophila, Yun Fan, Shiuan Wang, Jacob Hernandez, Vildan Betul Yenigun, Gillian Hertlein, Caitlin E. Fogarty, Jillian L. Lindblad, Andreas Bergmann Jan 2014

Genetic Models Of Apoptosis-Induced Proliferation Decipher Activation Of Jnk And Identify A Requirement Of Egfr Signaling For Tissue Regenerative Responses In Drosophila, Yun Fan, Shiuan Wang, Jacob Hernandez, Vildan Betul Yenigun, Gillian Hertlein, Caitlin E. Fogarty, Jillian L. Lindblad, Andreas Bergmann

University of Massachusetts Medical School Faculty Publications

Recent work in several model organisms has revealed that apoptotic cells are able to stimulate neighboring surviving cells to undergo additional proliferation, a phenomenon termed apoptosis-induced proliferation. This process depends critically on apoptotic caspases such as Dronc, the Caspase-9 ortholog in Drosophila, and may have important implications for tumorigenesis. While it is known that Dronc can induce the activity of Jun N-terminal kinase (JNK) for apoptosis-induced proliferation, the mechanistic details of this activation are largely unknown. It is also controversial if JNK activity occurs in dying or in surviving cells. Signaling molecules of the Wnt and BMP families have been ...


Oncogenic Ras Directs Silencing Of Tumor Suppressor Genes Through Ordered Recruitment Of Transcriptional Repressors, Narendra Wajapeyee, Sunil K. Malonia, Rajendra Kumar Palakurthy, Michael R. Green Oct 2013

Oncogenic Ras Directs Silencing Of Tumor Suppressor Genes Through Ordered Recruitment Of Transcriptional Repressors, Narendra Wajapeyee, Sunil K. Malonia, Rajendra Kumar Palakurthy, Michael R. Green

University of Massachusetts Medical School Faculty Publications

We previously identified 28 cofactors through which a RAS oncoprotein directs transcriptional silencing of Fas and other tumor suppressor genes (TSGs). Here we performed RNAi-based epistasis experiments and found that RAS-directed silencing occurs through a highly ordered pathway that is initiated by binding of ZFP354B, a sequence-specific DNA-binding protein, and culminates in recruitment of the DNA methyltransferase DNMT1. RNAi and pharmacological inhibition experiments reveal that silencing requires continuous function of RAS and its cofactors and can be rapidly reversed, which may have therapeutic implications for reactivation of silenced TSGs in RAS-positive cancers.


Cancer-Testis Gene Expression Is Associated With The Methylenetetrahydrofolate Reductase 677 C>T Polymorphism In Non-Small Cell Lung Carcinoma, Kerem M. Senses, Mithat Gonen, Ahmet Rasim Barutcu, Zeynep Kalaylioglu, Murat Isbilen, Ozlen Konu, Yao T. Chen, Nasser K. Altorki, Ali O. Gure Sep 2013

Cancer-Testis Gene Expression Is Associated With The Methylenetetrahydrofolate Reductase 677 C>T Polymorphism In Non-Small Cell Lung Carcinoma, Kerem M. Senses, Mithat Gonen, Ahmet Rasim Barutcu, Zeynep Kalaylioglu, Murat Isbilen, Ozlen Konu, Yao T. Chen, Nasser K. Altorki, Ali O. Gure

University of Massachusetts Medical School Faculty Publications

BACKGROUND: Tumor-specific, coordinate expression of cancer-testis (CT) genes, mapping to the X chromosome, is observed in more than 60% of non-small cell lung cancer (NSCLC) patients. Although CT gene expression has been unequivocally related to DNA demethylation of promoter regions, the underlying mechanism leading to loss of promoter methylation remains elusive. Polymorphisms of enzymes within the 1-carbon pathway have been shown to affect S-adenosyl methionine (SAM) production, which is the sole methyl donor in the cell. Allelic variants of several enzymes within this pathway have been associated with altered SAM levels either directly, or indirectly as reflected by altered levels ...


Sonic Hedgehog Mediates The Proliferation And Recruitment Of Transformed Mesenchymal Stem Cells To The Stomach, Jessica M. Donnelly, Ambreesh Chawla, Jeanmarie Houghton, Yana Zavros Sep 2013

Sonic Hedgehog Mediates The Proliferation And Recruitment Of Transformed Mesenchymal Stem Cells To The Stomach, Jessica M. Donnelly, Ambreesh Chawla, Jeanmarie Houghton, Yana Zavros

University of Massachusetts Medical School Faculty Publications

Studies using Helicobacter-infected mice show that bone marrow-derived mesenchymal stem cells (MSCs) can repopulate the gastric epithelium and promote gastric cancer progression. Within the tumor microenvironment of the stomach, pro-inflammatory cytokine interferon-gamma (IFNgamma) and Sonic hedgehog (Shh) are elevated. IFNgamma is implicated in tumor proliferation via activation of the Shh signaling pathway in various tissues but whether a similar mechanism exists in the stomach is unknown. We tested the hypothesis that IFNgamma drives MSC proliferation and recruitment, a response mediated by Shh signaling. The current study uses transplantation of an in vitro transformed mesenchymal stem cell line (stMSC(vect)), that ...


Mesenchymal Stem Cells Utilize Cxcr4-Sdf-1 Signaling For Acute, But Not Chronic, Trafficking To Gastric Mucosal Inflammation, Calin Stoicov, Hanchen Li, Jian Hua Liu, Jeanmarie Houghton Sep 2013

Mesenchymal Stem Cells Utilize Cxcr4-Sdf-1 Signaling For Acute, But Not Chronic, Trafficking To Gastric Mucosal Inflammation, Calin Stoicov, Hanchen Li, Jian Hua Liu, Jeanmarie Houghton

University of Massachusetts Medical School Faculty Publications

BACKGROUND: Helicobacter infection is the main risk factor in developing gastric cancer. Mesenchymal stem cells (MSCs) are non-hematopoietic stromal cells, which are able to differentiate into different cell lineages. MSC contribute to cancer development by forming the tumor directly, contributing to the microenvironment, or by promoting angiogenesis and metastasis. CXCR4/SDF-1 axis is used by MSC in trafficking, homing, and engraftment at chronic inflammation sites, and plays an important role in tumorigenesis.

AIM: To determine if CXCR4 receptor has a role in MSC contribution to the development of Helicobacter-mediated gastric cancer.

METHODS: SDF-1 and CXCR4 expression in mouse gastric mucosa ...


Molecular Signatures Of Chronic Myeloid Leukemia Stem Cells, Yaoyu Chen, Shaoguang Li Jun 2013

Molecular Signatures Of Chronic Myeloid Leukemia Stem Cells, Yaoyu Chen, Shaoguang Li

University of Massachusetts Medical School Faculty Publications

BCR-ABL tyrosine kinase inhibitors (TKIs) are effective in controlling Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) are unlikely to cure the disease because TKIs are unable to eradicate leukemia stem cells (LSCs) responsible for the disease relapse even after tyrosine kinase inhibition. In addition, the TKI resistance of LSCs is not associated with the BCR-ABL kinase domain mutations. These observations indicate that TKI-insensitive LSCs and TKI-sensitive leukemic progenitor cells are biologically different, which leads us to believe that LSCs and more differentiated leukemic cells have different genetic mechanisms. Further study of LSCs to identify the novel gene signatures and mechanisms that ...


Gli1 Regulates A Novel Neuropilin-2/Alpha6beta1 Integrin Based Autocrine Pathway That Contributes To Breast Cancer Initiation, Hira Lal Goel, Bryan M. Pursell, Cheng Chang, Leslie M. Shaw, Junhao Mao, Karl Simin, Prashant Kumar, Craig W. Vander Kooi, Leonard D. Shultz, Dale L. Greiner, Jens Henrik Norum, Rune Toftgard, Charlotte Kuperwasser, Arthur M. Mercurio Apr 2013

Gli1 Regulates A Novel Neuropilin-2/Alpha6beta1 Integrin Based Autocrine Pathway That Contributes To Breast Cancer Initiation, Hira Lal Goel, Bryan M. Pursell, Cheng Chang, Leslie M. Shaw, Junhao Mao, Karl Simin, Prashant Kumar, Craig W. Vander Kooi, Leonard D. Shultz, Dale L. Greiner, Jens Henrik Norum, Rune Toftgard, Charlotte Kuperwasser, Arthur M. Mercurio

University of Massachusetts Medical School Faculty Publications

The characterization of cells with tumour initiating potential is significant for advancing our understanding of cancer and improving therapy. Aggressive, triple-negative breast cancers (TNBCs) are enriched for tumour-initiating cells (TICs). We investigated that hypothesis that VEGF receptors expressed on TNBC cells mediate autocrine signalling that contributes to tumour initiation. We discovered the VEGF receptor neuropilin-2 (NRP2) is expressed preferentially on TICs, involved in the genesis of TNBCs and necessary for tumour initiation. The mechanism by which NRP2 signalling promotes tumour initiation involves stimulation of the alpha6beta1 integrin, focal adhesion kinase-mediated activation of Ras/MEK signalling and consequent expression of the ...


Atg6 Is Required For Multiple Vesicle Trafficking Pathways And Hematopoiesis In Drosophila, Bhupendra V. Shravage, Jahda H. Hill, Christine M. Powers, Louisa Wu, Eric H. Baehrecke Mar 2013

Atg6 Is Required For Multiple Vesicle Trafficking Pathways And Hematopoiesis In Drosophila, Bhupendra V. Shravage, Jahda H. Hill, Christine M. Powers, Louisa Wu, Eric H. Baehrecke

University of Massachusetts Medical School Faculty Publications

Atg6 (beclin 1 in mammals) is a core component of the Vps34 complex that is required for autophagy. Beclin 1 (Becn1) functions as a tumor suppressor, and Becn1(+/-) tumors in mice possess elevated cell stress and p62 levels, altered NF-kappaB signaling and genome instability. The tumor suppressor function of Becn1 has been attributed to its role in autophagy, and the potential functions of Atg6/Becn1 in other vesicle trafficking pathways for tumor development have not been considered. Here, we generate Atg6 mutant Drosophila and demonstrate that Atg6 is essential for autophagy, endocytosis and protein secretion. By contrast, the core autophagy ...


Human Papillomavirus E7 Induces Rereplication In Response To Dna Damage, Xueli Fan, Yingwang Liu, Susan Ann Heilman, Jason J. Chen Jan 2013

Human Papillomavirus E7 Induces Rereplication In Response To Dna Damage, Xueli Fan, Yingwang Liu, Susan Ann Heilman, Jason J. Chen

University of Massachusetts Medical School Faculty Publications

Human papillomavirus (HPV) infection is necessary but not sufficient for cervical carcinogenesis. Genomic instability caused by HPV allows cells to acquire additional mutations required for malignant transformation. Genomic instability in the form of polyploidy has been demonstrated to play an important role in cervical carcinogenesis. We have recently found that HPV-16 E7 oncogene induces polyploidy in response to DNA damage; however, the mechanism is not known. Here we present evidence demonstrating that HPV-16 E7-expressing cells have an intact G(2) checkpoint. Upon DNA damage, HPV-16 E7-expressing cells arrest at the G(2) checkpoint and then undergo rereplication, a process of ...