Research Topics
Genomes and Genes | Constantinos KoumenisSummaryAffiliation: Wake Forest University School of Medicine Country: USA Publications
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Publications
Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alphaConstantinos Koumenis
Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
Mol Cell Biol 22:7405-16. 2002....- Low oxygen stimulates the intellect. Symposium on hypoxia and development, physiology and diseaseConstantinos Koumenis
Department of Radiation Oncology, Cancer Biology and Neurosurgery, Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
EMBO Rep 7:679-84. 2006 
ER stress, hypoxia tolerance and tumor progressionConstantinos Koumenis
Department of Radiation Oncology, Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
Curr Mol Med 6:55-69. 2006..These results reveal a critical role for UPR activation for tumor cell resistance to hypoxia and tumor growth promotion and suggest that the UPR may be an attractive target for anti-tumor modalities...- Hypoxia and the unfolded protein responseConstantinos Koumenis
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Methods Enzymol 435:275-93. 2007.... 
Preferential cytotoxicity of bortezomib toward hypoxic tumor cells via overactivation of endoplasmic reticulum stress pathwaysDiane R Fels
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6072, USA
Cancer Res 68:9323-30. 2008....- Inhibition of fatty acid synthase induces endoplasmic reticulum stress in tumor cellsJoy L Little
Department of Cancer Biology, Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
Cancer Res 67:1262-9. 2007..These results provide the first evidence that FAS inhibitors induce ER stress and establish an important mechanistic link between FAS activity and ER function... - Disruption of crosstalk between the fatty acid synthesis and proteasome pathways enhances unfolded protein response signaling and cell deathJoy L Little
Department of Cancer Biology, Comprehensive Cancer Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC, USA
Mol Cancer Ther 7:3816-24. 2008..Combined, the data support the concept that the UPR balance between adaptive to stress signaling can be exploited to mediate increased cell death and suggests novel applications of FASN inhibitors for clinical use... - Arachidonic acid-induced gene expression in colon cancer cellsArta M Monjazeb
Department of Cancer Biology, Wake Forest University Baptist Medical Center, Winston-Salem, NC 27157, USA
Carcinogenesis 27:1950-60. 2006..Together, these studies reveal that the generation of intracellular AA and its subsequent impact on gene expression probably represents a critical step that regulates colon cancer cell proliferation... - ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growthMeixia Bi
Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
EMBO J 24:3470-81. 2005..Collectively, these findings demonstrate that activation of the ISR is required for tumor cell adaptation to hypoxia, and suggest that this pathway is an attractive target for antitumor modalities... - Tachpyridine, a metal chelator, induces G2 cell-cycle arrest, activates checkpoint kinases, and sensitizes cells to ionizing radiationJolyn Turner
Department of Biochemistry, Wake Forest University Health Scieces, Winston-Salem, NC 27157, USA
Blood 106:3191-9. 2005..Collectively, our results suggest that iron chelators may function as antitumor and radioenhancing agents and uncover a previously unexplored activity of iron chelators in activation of ATR and checkpoint kinases... - The PERK/eIF2alpha/ATF4 module of the UPR in hypoxia resistance and tumor growthDiane R Fels
Departments of Radiation Oncology, Cancer Biology and Neurosurgery, Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA
Cancer Biol Ther 5:723-8. 2006.... - The chemopreventive agent curcumin is a potent radiosensitizer of human cervical tumor cells via increased reactive oxygen species production and overactivation of the mitogen-activated protein kinase pathwayPrashanthi Javvadi
Department of Radiation Oncology, University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, PA 19104, USA
Mol Pharmacol 73:1491-501. 2008.... - ATF4, an ER stress and hypoxia-inducible transcription factor and its potential role in hypoxia tolerance and tumorigenesisJiangbin Ye
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Curr Mol Med 9:411-6. 2009..Here we summarize recent findings regarding the regulation of ATF4 in transformed cells, clinical tumor samples and tumor models, and speculate on its potential role in tumor progression and chemoresistance... - Effects of radiation quality and oxygen on clustered DNA lesions and cell deathRobert D Stewart
Department of Radiation Oncology, University of Washington, Seattle, Washington 98195 6043, USA
Radiat Res 176:587-602. 2011..Information from Monte Carlo simulations of cluster induction may also prove useful for efforts to better exploit radiation quality and reduce the impact of tumor hypoxia in proton and carbon-ion radiation therapy... - The adenoviral E4orf6 protein induces atypical apoptosis in response to DNA damageLori S Hart
Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
J Biol Chem 282:6061-7. 2007..The function of E4orf6 as an inhibitor of PP2A and activator of PARP in the absence of other adenoviral gene products is of importance in delineating the adenovirus-host cell interplay... - The chemopreventive and clinically used agent curcumin sensitizes HPV (-) but not HPV (+) HNSCC to ionizing radiation, in vitro and in a mouse orthotopic modelSTEPHEN TUTTLE
Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Cancer Biol Ther 13:575-84. 2012..We therefore propose that curcumin and RT should be considered as a first line treatment of HPV (-) HNSCC... - The GCN2-ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivationJiangbin Ye
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
EMBO J 29:2082-96. 2010..We conclude that the GCN2-eIF2alpha-ATF4 pathway is critical for maintaining metabolic homeostasis in tumour cells, making it a novel and attractive target for anti-tumour approaches... - Controlled cell killing by a recombinant nonsegmented negative-strand RNA virusGriffith D Parks
Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157 1064, USA
Virology 293:192-203. 2002..Our results demonstrating controlled cell killing by a recombinant paramyxovirus support the use of negative-strand RNA viruses as therapeutic vectors for targeted killing of cancer cells... - Human colon cancer stem cells are enriched by insulin-like growth factor-1 and are sensitive to figitumumabLori S Hart
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
Cell Cycle 10:2331-8. 2011..Our results suggest that CP-751,871 has preferential activity against putative CSC populations and, therefore, may complement current standard chemotherapeutic regimens that target cycling cells... - Identification and biological evaluation of a novel and potent small molecule radiation sensitizer via an unbiased screen of a chemical libraryBrian E Lally
Department of Radiation Oncology, Wake Forest University Health Sciences, Winston Salem, North Carolina, USA
Cancer Res 67:8791-9. 2007..These results show the potential of this cell-based, high-throughput screening method to identify novel radiosensitizers and suggest that NS-123 and similar nitrophenol compounds may be effective in antiglioma modalities... - 19-nor-1 alpha,25-dihydroxyvitamin D2 (paricalcitol) inhibits the proliferation of human pancreatic cancer cells in vitro and in vivoGary G Schwartz
Department of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
Cancer Biol Ther 7:430-6. 2008..Tumor inhibition was accompanied by in vivo upregulation of p21 and p27 expression. Given the few therapeutic options for patients with pancreatic cancer, further exploration of paricalcitol, an FDA-approved medication, is warranted... - Location, location, location-makes all the difference for hypoxia in lung tumorsAmit Maity
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, 19104 6072, USA
Clin Cancer Res 16:4685-7. 2010..Here, we describe how different animal tumor models of lung cancer can yield surprisingly different hypoxic profiles... - Inhibitors of arachidonic acid metabolism act synergistically to signal apoptosis in neoplastic cellsArta M Monjazeb
Department of Cancer Biology, Wake Forest University Baptist Medical Center, Winston-Salem, NC 27157, USA
Prostaglandins Leukot Essent Fatty Acids 73:463-74. 2005..Further study is required to determine the downstream pathway(s) whereby high cellular burdens of unesterified AA promote apoptosis... - Dual PI3K/mTOR inhibitor NVP-BEZ235 suppresses hypoxia-inducible factor (HIF)-1α expression by blocking protein translation and increases cell death under hypoxiaJayashree Karar
Department of Radiation Oncology, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA
Cancer Biol Ther 13:1102-11. 2012..In conclusion, we have found that BEZ235 blocks HIF-1α induction by decreasing protein translation and increases cell killing under hypoxia, likely by increasing apoptosis... - ER stress-mediated autophagy promotes Myc-dependent transformation and tumor growthLori S Hart
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 5156, USA
J Clin Invest 122:4621-34. 2012..Our findings establish a role for UPR as an enhancer of c-Myc-induced transformation and suggest that UPR inhibition may be particularly effective against malignancies characterized by c-Myc overexpression... - HIF and MIF--a nifty way to delay senescence?Amit Maity
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Genes Dev 20:3337-41. 2006 - In vivo profiling of hypoxic gene expression in gliomas using the hypoxia marker EF5 and laser-capture microdissectionDiane Marotta
Department of Radiation Oncology, University of Pennsylvania, Pennsylvania, USA
Cancer Res 71:779-89. 2011.... - HIF-1alpha and p53: the ODD couple?Diane R Fels
Department of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
Trends Biochem Sci 30:426-9. 2005..The article identifies potential structural parameters required for this interaction and suggests an alternative mechanism by which p53 might impact tumor response to therapy... - Pancreatic cancer cells express 25-hydroxyvitamin D-1 alpha-hydroxylase and their proliferation is inhibited by the prohormone 25-hydroxyvitamin D3Gary G Schwartz
Department of Cancer Biology, Comprehensive Cancer Center of Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
Carcinogenesis 25:1015-26. 2004.... - The adenovirus E4orf6 protein inhibits DNA double strand break repair and radiosensitizes human tumor cells in an E1B-55K-independent mannerLori S Hart
Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA
J Biol Chem 280:1474-81. 2005.... - p27Kip1 is essential for the antiproliferative action of 1,25-dihydroxyvitamin D3 in primary, but not immortalized, mouse embryonic fibroblastsWendy N Wade
Department of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
J Biol Chem 277:37301-6. 2002..05), respectively). These data from primary and immortalized MEFs demonstrate that there are both p27-dependent and -independent pathways that mediate the antiproliferative action of 1,25(OH)(2)D(3)... - Gene expression during acute and prolonged hypoxia is regulated by distinct mechanisms of translational controlMarianne Koritzinsky
Department of Radiation Oncology (MAASTRO, GROW Research Institute, University of Maastricht, The Netherlands
EMBO J 25:1114-25. 2006..Together, our data indicate that acute and prolonged hypoxia regulates mRNA translation through distinct mechanisms, each with important contributions to hypoxic gene expression... - "Translating" tumor hypoxia: unfolded protein response (UPR)-dependent and UPR-independent pathwaysConstantinos Koumenis
Department of Radiation Oncology, Maastricht Radiation Oncology (Maastro) Laboratory, GROW Research Institute, USN50/23 University of Maastricht, The Netherlands
Mol Cancer Res 4:423-36. 2006..Thus, the severity and duration of hypoxia can lead to different biological and therapeutic consequences... - Control of the hypoxic response through regulation of mRNA translationBradly G Wouters
Department of Radiation Oncology, Maastricht Radiation Oncology MaastRO Lab, GROW Research Institute, USN50 23 University of Maastricht, P O Box 616, 6200MD Maastricht, The Netherlands
Semin Cell Dev Biol 16:487-501. 2005..Consequently, both arms of translational control during hypoxia influence hypoxia induced gene expression and the hypoxic phenotype...