Constantinos Koumenis

Summary

Affiliation: Wake Forest University School of Medicine
Country: USA

Publications

  1. pmc Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha
    Constantinos Koumenis
    Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    Mol Cell Biol 22:7405-16. 2002
  2. pmc Low oxygen stimulates the intellect. Symposium on hypoxia and development, physiology and disease
    Constantinos 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
  3. ncbi ER stress, hypoxia tolerance and tumor progression
    Constantinos 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
  4. ncbi Hypoxia and the unfolded protein response
    Constantinos Koumenis
    Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Methods Enzymol 435:275-93. 2007
  5. pmc Preferential cytotoxicity of bortezomib toward hypoxic tumor cells via overactivation of endoplasmic reticulum stress pathways
    Diane R Fels
    Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6072, USA
    Cancer Res 68:9323-30. 2008
  6. pmc Inhibition of autophagy as a strategy to augment radiosensitization by the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235
    George J Cerniglia
    Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Pharmacol 82:1230-40. 2012
  7. ncbi Inhibition of fatty acid synthase induces endoplasmic reticulum stress in tumor cells
    Joy 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
  8. pmc Disruption of crosstalk between the fatty acid synthesis and proteasome pathways enhances unfolded protein response signaling and cell death
    Joy 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
  9. ncbi Arachidonic acid-induced gene expression in colon cancer cells
    Arta M Monjazeb
    Department of Cancer Biology, Wake Forest University Baptist Medical Center, Winston Salem, NC 27157, USA
    Carcinogenesis 27:1950-60. 2006
  10. pmc ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth
    Meixia Bi
    Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    EMBO J 24:3470-81. 2005

Collaborators

Detail Information

Publications38

  1. pmc Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha
    Constantinos Koumenis
    Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    Mol Cell Biol 22:7405-16. 2002
    ....
  2. pmc Low oxygen stimulates the intellect. Symposium on hypoxia and development, physiology and disease
    Constantinos 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
  3. ncbi ER stress, hypoxia tolerance and tumor progression
    Constantinos 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...
  4. ncbi Hypoxia and the unfolded protein response
    Constantinos Koumenis
    Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Methods Enzymol 435:275-93. 2007
    ....
  5. pmc Preferential cytotoxicity of bortezomib toward hypoxic tumor cells via overactivation of endoplasmic reticulum stress pathways
    Diane R Fels
    Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6072, USA
    Cancer Res 68:9323-30. 2008
    ....
  6. pmc Inhibition of autophagy as a strategy to augment radiosensitization by the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235
    George J Cerniglia
    Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Pharmacol 82:1230-40. 2012
    ..Our data offer a rationale for combining NVP-BEZ235 along with an autophagy inhibitor (i.e., chloroquine) and radiation in future clinical trials...
  7. ncbi Inhibition of fatty acid synthase induces endoplasmic reticulum stress in tumor cells
    Joy 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...
  8. pmc Disruption of crosstalk between the fatty acid synthesis and proteasome pathways enhances unfolded protein response signaling and cell death
    Joy 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...
  9. ncbi Arachidonic acid-induced gene expression in colon cancer cells
    Arta 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...
  10. pmc ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth
    Meixia 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...
  11. pmc Identification and characterization of a potent activator of p53-independent cellular senescence via a small-molecule screen for modifiers of the integrated stress response
    Carly M Sayers
    Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Translational Research Center Room 8 124, 3400 Civic Center Blvd, Bldg 421, Philadelphia, PA 19104 5156, USA
    Mol Pharmacol 83:594-604. 2013
    ..Induction of γ-H2AX was abrogated in ATF4 knockdown cells. Together, these results suggest that modulation of the ISR pathway with the small molecule E235 could be a promising antitumor strategy...
  12. pmc Tachpyridine, a metal chelator, induces G2 cell-cycle arrest, activates checkpoint kinases, and sensitizes cells to ionizing radiation
    Jolyn 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...
  13. ncbi The PERK/eIF2alpha/ATF4 module of the UPR in hypoxia resistance and tumor growth
    Diane 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
    ....
  14. pmc Dual PI3K/mTOR inhibitor NVP-BEZ235 suppresses hypoxia-inducible factor (HIF)-1α expression by blocking protein translation and increases cell death under hypoxia
    Jayashree 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...
  15. ncbi Effects of radiation quality and oxygen on clustered DNA lesions and cell death
    Robert 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...
  16. pmc 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 pathway
    Prashanthi Javvadi
    Department of Radiation Oncology, University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, PA 19104, USA
    Mol Pharmacol 73:1491-501. 2008
    ....
  17. ncbi ATF4, an ER stress and hypoxia-inducible transcription factor and its potential role in hypoxia tolerance and tumorigenesis
    Jiangbin 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...
  18. pmc ER stress-mediated autophagy promotes Myc-dependent transformation and tumor growth
    Lori 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...
  19. ncbi The adenoviral E4orf6 protein induces atypical apoptosis in response to DNA damage
    Lori 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...
  20. doi The chemopreventive and clinically used agent curcumin sensitizes HPV (-) but not HPV (+) HNSCC to ionizing radiation, in vitro and in a mouse orthotopic model
    STEPHEN 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...
  21. pmc The GCN2-ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivation
    Jiangbin 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...
  22. ncbi Controlled cell killing by a recombinant nonsegmented negative-strand RNA virus
    Griffith 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...
  23. pmc Human colon cancer stem cells are enriched by insulin-like growth factor-1 and are sensitive to figitumumab
    Lori 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...
  24. pmc Location, location, location-makes all the difference for hypoxia in lung tumors
    Amit 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...
  25. ncbi 19-nor-1 alpha,25-dihydroxyvitamin D2 (paricalcitol) inhibits the proliferation of human pancreatic cancer cells in vitro and in vivo
    Gary 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...
  26. pmc Identification and biological evaluation of a novel and potent small molecule radiation sensitizer via an unbiased screen of a chemical library
    Brian 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...
  27. ncbi Inhibitors of arachidonic acid metabolism act synergistically to signal apoptosis in neoplastic cells
    Arta 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...
  28. pmc The heat shock proteins as targets for radiosensitization and chemosensitization in cancer
    David M Guttmann
    Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    Cancer Biol Ther 12:1023-31. 2011
    ..We focus on attempts to target these proteins, particularly the small HSPs, in developing potent radiation and chemotherapy sensitizers, as well as proposed mechanisms for this sensitization effect...
  29. pmc PERK-ing up autophagy during MYC-induced tumorigenesis
    Souvik Dey
    Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    Autophagy 9:612-4. 2013
    ..Our findings demonstrate that the EIF2AK3/PERK-EIF2S1/eIF2α-ATF4 arm of the UPR promotes tumorigenesis by activating autophagy and enhancing tumor formation. Therefore, the UPR is an attractive target in MYC-driven cancers...
  30. pmc In vivo profiling of hypoxic gene expression in gliomas using the hypoxia marker EF5 and laser-capture microdissection
    Diane Marotta
    Department of Radiation Oncology, University of Pennsylvania, Pennsylvania, USA
    Cancer Res 71:779-89. 2011
    ....
  31. ncbi 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...
  32. ncbi 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
  33. ncbi Pancreatic cancer cells express 25-hydroxyvitamin D-1 alpha-hydroxylase and their proliferation is inhibited by the prohormone 25-hydroxyvitamin D3
    Gary 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
    ....
  34. ncbi The adenovirus E4orf6 protein inhibits DNA double strand break repair and radiosensitizes human tumor cells in an E1B-55K-independent manner
    Lori 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
    ....
  35. ncbi p27Kip1 is essential for the antiproliferative action of 1,25-dihydroxyvitamin D3 in primary, but not immortalized, mouse embryonic fibroblasts
    Wendy 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)...
  36. ncbi "Translating" tumor hypoxia: unfolded protein response (UPR)-dependent and UPR-independent pathways
    Constantinos 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...
  37. pmc Gene expression during acute and prolonged hypoxia is regulated by distinct mechanisms of translational control
    Marianne 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...
  38. ncbi Control of the hypoxic response through regulation of mRNA translation
    Bradly 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...