Thomas H Bugge

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. ncbi request reprint Matriptase-dependent cell surface proteolysis in epithelial development and pathogenesis
    Thomas H Bugge
    Proteases and Tissue Remodeling Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    Front Biosci 12:5060-70. 2007
  2. pmc Suppression of Tumorigenicity-14, encoding matriptase, is a critical suppressor of colitis and colitis-associated colon carcinogenesis
    P Kosa
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    Oncogene 31:3679-95. 2012
  3. pmc c-Met-induced epithelial carcinogenesis is initiated by the serine protease matriptase
    R Szabo
    Oral and Pharyngeal Cancer Branch, NIDCR, NIH, Bethesda, MD 20892, USA
    Oncogene 30:2003-16. 2011
  4. pmc Matriptase: potent proteolysis on the cell surface
    Karin List
    Proteases and Tissue Remodeling Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Med 12:1-7. 2006
  5. pmc Type II transmembrane serine proteases
    Thomas H Bugge
    Proteases and Tissue Remodeling Section, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 284:23177-81. 2009
  6. pmc Delineation of matriptase protein expression by enzymatic gene trapping suggests diverging roles in barrier function, hair formation, and squamous cell carcinogenesis
    Karin List
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA
    Am J Pathol 168:1513-25. 2006
  7. pmc Potent inhibition and global co-localization implicate the transmembrane Kunitz-type serine protease inhibitor hepatocyte growth factor activator inhibitor-2 in the regulation of epithelial matriptase activity
    Roman Szabo
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 283:29495-504. 2008
  8. pmc Epithelial integrity is maintained by a matriptase-dependent proteolytic pathway
    Karin List
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA
    Am J Pathol 175:1453-63. 2009
  9. ncbi request reprint Mouse DESC1 is located within a cluster of seven DESC1-like genes and encodes a type II transmembrane serine protease that forms serpin inhibitory complexes
    John P Hobson
    Proteases and Tissue Remodeling Unit, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 279:46981-94. 2004
  10. pmc Matrix metalloproteinase-activated anthrax lethal toxin demonstrates high potency in targeting tumor vasculature
    Shihui Liu
    Laboratory of Bacterial Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Biol Chem 283:529-40. 2008

Collaborators

Detail Information

Publications86

  1. ncbi request reprint Matriptase-dependent cell surface proteolysis in epithelial development and pathogenesis
    Thomas H Bugge
    Proteases and Tissue Remodeling Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    Front Biosci 12:5060-70. 2007
    ..Matriptase activity must be tightly controlled in epithelial tissues by transcriptional and posttranslational mechanisms, as matriptase dysregulation can cause embryonic demise as well as malignant transformation...
  2. pmc Suppression of Tumorigenicity-14, encoding matriptase, is a critical suppressor of colitis and colitis-associated colon carcinogenesis
    P Kosa
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    Oncogene 31:3679-95. 2012
    ....
  3. pmc c-Met-induced epithelial carcinogenesis is initiated by the serine protease matriptase
    R Szabo
    Oral and Pharyngeal Cancer Branch, NIDCR, NIH, Bethesda, MD 20892, USA
    Oncogene 30:2003-16. 2011
    ..The study provides a specific example of how epithelial transformation can be promoted by epigenetic acquisition of the capacity to convert a widely available paracrine growth factor precursor to its signaling competent state...
  4. pmc Matriptase: potent proteolysis on the cell surface
    Karin List
    Proteases and Tissue Remodeling Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Med 12:1-7. 2006
    ..Matriptase and HAI expression are frequently dysregulated in human cancer, and matriptase expression that is unopposed by HAI-1 potently promotes carcinogenesis and metastatic dissemination in animal models...
  5. pmc Type II transmembrane serine proteases
    Thomas H Bugge
    Proteases and Tissue Remodeling Section, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 284:23177-81. 2009
    ..Progress has also been made in identifying molecular substrates and endogenous inhibitors. This minireview summarizes the current knowledge of the rapidly advancing TTSP field...
  6. pmc Delineation of matriptase protein expression by enzymatic gene trapping suggests diverging roles in barrier function, hair formation, and squamous cell carcinogenesis
    Karin List
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA
    Am J Pathol 168:1513-25. 2006
    ..Combined with previous studies, these data suggest that matriptase has diverging functions in the genesis of stratified keratinized epithelium, hair follicles, and squamous cell carcinoma...
  7. pmc Potent inhibition and global co-localization implicate the transmembrane Kunitz-type serine protease inhibitor hepatocyte growth factor activator inhibitor-2 in the regulation of epithelial matriptase activity
    Roman Szabo
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 283:29495-504. 2008
    ..Unlike HAI-1 and matriptase, however, HAI-2 expression was also detected in non-epithelial cells of brain and lymph nodes, suggesting that HAI-2 may also be involved in inhibition of serine proteases other than matriptase...
  8. pmc Epithelial integrity is maintained by a matriptase-dependent proteolytic pathway
    Karin List
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA
    Am J Pathol 175:1453-63. 2009
    ....
  9. ncbi request reprint Mouse DESC1 is located within a cluster of seven DESC1-like genes and encodes a type II transmembrane serine protease that forms serpin inhibitory complexes
    John P Hobson
    Proteases and Tissue Remodeling Unit, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 279:46981-94. 2004
    ..Together, these data show that mouse DESC1 encodes a functional cell surface serine protease that may have important functions in the epidermis, oral, and reproductive epithelium...
  10. pmc Matrix metalloproteinase-activated anthrax lethal toxin demonstrates high potency in targeting tumor vasculature
    Shihui Liu
    Laboratory of Bacterial Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Biol Chem 283:529-40. 2008
    ..Moreover, the modified toxin also displayed lower immunogenicity compared with the wild-type toxin. All these properties suggest that this MMP-activated anti-tumor toxin has potential for use in cancer therapy...
  11. ncbi request reprint Autosomal ichthyosis with hypotrichosis syndrome displays low matriptase proteolytic activity and is phenocopied in ST14 hypomorphic mice
    Karin List
    Oral and Pharyngeal Cancer Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 282:36714-23. 2007
    ....
  12. pmc A matriptase-prostasin reciprocal zymogen activation complex with unique features: prostasin as a non-enzymatic co-factor for matriptase activation
    Stine Friis
    Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 288:19028-39. 2013
    ....
  13. pmc Deregulated matriptase causes ras-independent multistage carcinogenesis and promotes ras-mediated malignant transformation
    Karin List
    Proteases and Tissue Remodeling Unit, Molecular Carcinogenesis Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA
    Genes Dev 19:1934-50. 2005
    ..Increasing epidermal HAI-1 expression completely negated the oncogenic effects of matriptase. The data implicate dysregulated matriptase expression in malignant epithelial transformation...
  14. pmc Loss of proteolytically processed filaggrin caused by epidermal deletion of Matriptase/MT-SP1
    Karin List
    Proteases and Tissue Remodeling Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 163:901-10. 2003
    ..The data identify keratinocyte Matriptase/MT-SP1 as an essential component of the profilaggrin-processing pathway and a key regulator of terminal epidermal differentiation...
  15. pmc M2-like macrophages are responsible for collagen degradation through a mannose receptor-mediated pathway
    Daniel H Madsen
    Proteases and Tissue Remodeling Section and 2 Intracellular Membrane Trafficking Unit, Oral and Pharyngeal Cancer Branch, and 3 Matrix Metalloproteinase Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892
    J Cell Biol 202:951-66. 2013
    ..This study demonstrates the importance of receptor-mediated cellular uptake to collagen turnover in vivo and identifies a key role of M2-like macrophages in this process. ..
  16. pmc Complementary roles of intracellular and pericellular collagen degradation pathways in vivo
    Rebecca A Wagenaar-Miller
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Room 211, Bethesda, MD 20892, USA
    Mol Cell Biol 27:6309-22. 2007
    ..These findings have important implications for the use of pharmacological inhibitors of collagenase activity to prevent connective tissue destruction in a variety of diseases...
  17. pmc Loss of matriptase suppression underlies spint1 mutation-associated ichthyosis and postnatal lethality
    Roman Szabo
    Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Room 211, Bethesda, MD 20892, USA
    Am J Pathol 174:2015-22. 2009
    ..This study identifies matriptase suppression as an essential function of HAI-1 in postnatal tissue homeostasis...
  18. pmc Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation
    Brian M Connolly
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 116:1593-603. 2010
    ....
  19. pmc Intracellular collagen degradation mediated by uPARAP/Endo180 is a major pathway of extracellular matrix turnover during malignancy
    Alejandro C Curino
    Proteases and Tissue Remodeling Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 169:977-85. 2005
    ..These studies identify uPARAP/Endo180 as a key mediator of collagen turnover in a pathophysiological context...
  20. pmc Expression and genetic loss of function analysis of the HAT/DESC cluster proteases TMPRSS11A and HAT
    Katiuchia Uzzun Sales
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 6:e23261. 2011
    ....
  21. pmc Regulation of cell surface protease matriptase by HAI2 is essential for placental development, neural tube closure and embryonic survival in mice
    Roman Szabo
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    Development 136:2653-63. 2009
    ..This study indicates that unregulated matriptase-dependent cell surface proteolysis can cause a diverse array of abnormalities in mammalian development...
  22. pmc Reduced prostasin (CAP1/PRSS8) activity eliminates HAI-1 and HAI-2 deficiency-associated developmental defects by preventing matriptase activation
    Roman Szabo
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Genet 8:e1002937. 2012
    ....
  23. pmc Matriptase-deficient mice exhibit ichthyotic skin with a selective shift in skin microbiota
    Tiffany C Scharschmidt
    National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA
    J Invest Dermatol 129:2435-42. 2009
    ..St14(hypo/-) mice provide early evidence that the cutaneous microbiome can be specifically altered by genetic state, which may play an important role in modulating skin disease...
  24. pmc Dissecting the urokinase activation pathway using urokinase-activated anthrax toxin
    Shihui Liu
    Laboratory of Bacterial Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
    Methods Mol Biol 539:175-90. 2009
    ..The results demonstrate that both uPAR and plasminogen play critical roles in pro-uPA activation both in vitro and in vivo...
  25. pmc Matriptase-3 is a novel phylogenetically preserved membrane-anchored serine protease with broad serpin reactivity
    Roman Szabo
    Proteases and Tissue Remodeling Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Bethesda, MD 20892, USA
    Biochem J 390:231-42. 2005
    ..Our study identifies matriptase-3 as a novel biologically active TTSP of the matriptase subfamily having a unique expression pattern and post-translational regulation...
  26. pmc Matriptase initiates activation of epidermal pro-kallikrein and disease onset in a mouse model of Netherton syndrome
    Katiuchia Uzzun Sales
    National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA
    Nat Genet 42:676-83. 2010
    ..These results uncover a pathogenic matriptase-pro-kallikrein pathway that could operate in several human skin and inflammatory diseases...
  27. pmc Efficient targeting of head and neck squamous cell carcinoma by systemic administration of a dual uPA and MMP-activated engineered anthrax toxin
    Jeffrey M Schafer
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 6:e20532. 2011
    ..This intercomplementing toxin warrants further investigation as an anti-HNSCC agent...
  28. pmc A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo
    Michael P Motley
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD
    Blood 127:1085-96. 2016
    ..The study identifies a novel fibrin endocytic pathway engaged in extravascular fibrin clearance and shows that interstitial fibrin and collagen are cleared by different subsets of macrophages employing distinct molecular pathways. ..
  29. pmc Detection of active matriptase using a biotinylated chloromethyl ketone peptide
    Sine Godiksen
    Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark Department of Biology, University of Copenhagen, Copenhagen, Denmark Proteases and Tissue Remodeling Unit, National Institute of Dental and Craniofacial Research, Bethesda, Maryland, United States of America
    PLoS ONE 8:e77146. 2013
    ..This study presents a novel assay for detection of enzymatically active matriptase in living human and murine cells. The assay can be applied to a variety of cell systems and species. ..
  30. pmc uPARAP/Endo180 is essential for cellular uptake of collagen and promotes fibroblast collagen adhesion
    Lars H Engelholm
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 160:1009-15. 2003
    ..These studies identify a central function of uPARAP/Endo180 in cellular collagen interactions...
  31. pmc Capillary morphogenesis protein-2 is required for mouse parturition by maintaining uterine collagen homeostasis
    Diane E Peters
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA
    Biochem Biophys Res Commun 422:393-7. 2012
    ..In parallel to its role in anthrax toxin binding and internalization, herein we provide evidence that CMG2 may function as a collagen receptor which is essential for maintaining collagen homeostasis in the uterus...
  32. ncbi request reprint Imaging specific cell-surface proteolytic activity in single living cells
    John P Hobson
    Proteases and Tissue Remodeling Unit, National Institute of Dental and Craniofacial Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 30 Convent Drive, Bethesda, Maryland 20892, USA
    Nat Methods 3:259-61. 2006
    ..We have adapted the assay for fluorescence microscopy, flow cytometry and fluorescent plate reader formats, and it is amenable for automation and high-throughput analysis...
  33. pmc Intermolecular complementation achieves high-specificity tumor targeting by anthrax toxin
    Shihui Liu
    Microbial Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
    Nat Biotechnol 23:725-30. 2005
    ..These results show that anthrax toxin, and by implication other multimeric toxins, offer excellent opportunities to introduce multiple-specificity determinants and thereby achieve high therapeutic indices...
  34. ncbi request reprint Co-localization of the channel activating protease prostasin/(CAP1/PRSS8) with its candidate activator, matriptase
    Karin List
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Cell Physiol 213:237-45. 2007
    ..These data suggest that a matriptase-prostasin zymogen activation cascade may be functionally operative in multiple epithelial tissues, but matriptase promotes epithelial carcinogenesis independent of prostasin...
  35. pmc Regulation of feto-maternal barrier by matriptase- and PAR-2-mediated signaling is required for placental morphogenesis and mouse embryonic survival
    Roman Szabo
    Proteases and Tissue Remodeling Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Genet 10:e1004470. 2014
    ..Our results reveal unexpected complementary roles of matriptase-prostasin- and PAR-2-dependent proteolytic signaling in the establishment of placental epithelial barrier function and overall embryonic survival. ..
  36. pmc The membrane-anchored serine protease prostasin (CAP1/PRSS8) supports epidermal development and postnatal homeostasis independent of its enzymatic activity
    Diane E Peters
    From the Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, the Program of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts 02111
    J Biol Chem 289:14740-9. 2014
    ..This study provides the first demonstration that essential in vivo functions of prostasin are executed by a non-enzymatic activity of this unique membrane-anchored serine protease. ..
  37. ncbi request reprint Anthrax toxin: structures, functions and tumour targeting
    Shihui Liu
    Microbial Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Expert Opin Biol Ther 3:843-53. 2003
    ....
  38. ncbi request reprint Increased expression of the collagen internalization receptor uPARAP/Endo180 in the stroma of head and neck cancer
    Jay Sulek
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    J Histochem Cytochem 55:347-53. 2007
    ..These data suggest that uPARAP/Endo180 participates in the connective tissue destruction during head and neck squamous cell carcinoma progression by mediating cellular uptake and lysosomal degradation of collagen...
  39. pmc PDZ-RhoGEF and LARG are essential for embryonic development and provide a link between thrombin and LPA receptors and Rho activation
    Constantinos M Mikelis
    Oral and Pharyngeal Cancer Branch, NIDCR, Genetics and Developmental Biology Center, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 288:12232-43. 2013
    ..These findings provide evidence of an essential role for the RGS-containing RhoGEF family in signaling to Rho by Gα12/13-coupled GPCRs, which may likely play a critical role during embryonic development...
  40. pmc Accelerated wound healing by mTOR activation in genetically defined mouse models
    Cristiane H Squarize
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 5:e10643. 2010
    ..Here, we exploited this emerging information to search for novel molecular targets to accelerate wound healing...
  41. ncbi request reprint Type II transmembrane serine proteases
    Roman Szabo
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    Thromb Haemost 90:185-93. 2003
    ..The knowledge gathered thus far of the genetics, physiology, and pathology of this interesting new serine protease family will be reviewed here in brief...
  42. pmc Solid tumor therapy by selectively targeting stromal endothelial cells
    Shihui Liu
    Microbial Pathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892
    Proc Natl Acad Sci U S A 113:E4079-87. 2016
    ..The ability to give repeated doses of toxins, coupled with the specific targeting of tumor endothelial cells, suggests that our strategy should be efficacious for a wide range of solid tumors. ..
  43. pmc Delineation of proteolytic and non-proteolytic functions of the membrane-anchored serine protease prostasin
    Roman Szabo
    Proteases and Tissue Remodeling Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    Development 143:2818-28. 2016
    ....
  44. pmc Anthrax Toxin Protective Antigen Variants That Selectively Utilize either the CMG2 or TEM8 Receptors for Cellular Uptake and Tumor Targeting
    Kuang Hua Chen
    From the Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892 3202 and
    J Biol Chem 291:22021-22029. 2016
    ..The structural basis of the alterations in the receptor binding activities of these mutants is also discussed...
  45. pmc Potent antitumor activity of a urokinase-activated engineered anthrax toxin
    Shihui Liu
    Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 100:657-62. 2003
    ..This tumoricidal activity depended strictly on tumor cell-surface plasminogen activation. The data show that a simple change of protease activation specificity converts anthrax toxin from a highly lethal to a potent tumoricidal agent...
  46. pmc Role for the actomyosin complex in regulated exocytosis revealed by intravital microscopy
    Andrius Masedunskas
    Intracellular Membrane Trafficking Unit and Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892 4340, USA
    Proc Natl Acad Sci U S A 108:13552-7. 2011
    ..Our results provide information on the machinery controlling regulated secretion and show that intravital microscopy provides unique opportunities to address fundamental questions in cell biology under physiological conditions...
  47. pmc Membrane-anchored serine proteases in health and disease
    Toni M Antalis
    Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, Maryland, USA
    Prog Mol Biol Transl Sci 99:1-50. 2011
    ..This chapter reviews our current knowledge of the biological and physiological functions of these proteases, their molecular substrates, and their contributions to disease...
  48. pmc Conditional deletion of neuronal cyclin-dependent kinase 5 in developing forebrain results in microglial activation and neurodegeneration
    Satoru Takahashi
    Functional Genomics Section, Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA
    Am J Pathol 176:320-9. 2010
    ....
  49. pmc Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities
    Diane E Peters
    Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA Program of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA, USA
    Toxicol Appl Pharmacol 279:220-9. 2014
    ..This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. ..
  50. pmc Differential actions of the endocytic collagen receptor uPARAP/Endo180 and the collagenase MMP-2 in bone homeostasis
    Daniel H Madsen
    The Finsen Laboratory, Rigshospitalet Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark
    PLoS ONE 8:e71261. 2013
    ..We conclude that both uPARAP and MMP-2 take part in matrix turnover processes important for bone growth. However, in some physiological situations, these two components do not support the same step in the growth process. ..
  51. pmc Membrane-anchored serine proteases in vertebrate cell and developmental biology
    Roman Szabo
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA
    Annu Rev Cell Dev Biol 27:213-35. 2011
    ..Particularly highlighted is how the study of membrane-anchored serine proteases has expanded our knowledge of the range of physiological processes that require regulated proteolysis at the cell surface...
  52. doi request reprint Type II transmembrane serine proteases in development and disease
    Roman Szabo
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States
    Int J Biochem Cell Biol 40:1297-316. 2008
    ..This review presents our current knowledge of the biological functions of the individual TTSPs in mouse and human tissue development and disease...
  53. ncbi request reprint MT1-MMP controls tumor-induced angiogenesis through the release of semaphorin 4D
    John R Basile
    Oral and Pharyngeal Cancer Branch and Matrix Metalloproteinase Unit, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 282:6899-905. 2007
    ..These results suggest that the proteolytic cleavage of Semaphorin 4D may provide a novel molecular mechanism by which membrane type 1-matrix metalloproteinase controls tumor-induced angiogenesis...
  54. pmc Distinct Developmental Functions of Prostasin (CAP1/PRSS8) Zymogen and Activated Prostasin
    Stine Friis
    From the Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, the Section for Molecular Disease Biology, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, DK 2100 Copenhagen, Denmark, and
    J Biol Chem 291:2577-82. 2016
    ....
  55. pmc An anthrax toxin variant with an improved activity in tumor targeting
    Alexander N Wein
    Microbial Pathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
    Sci Rep 5:16267. 2015
    ..Consequently, the new combination of PA-L1-I207R and PA-U2-R200A showed potent anti-tumor activity and low toxicity, exceeding the performance of the original combination, and warranting further investigation. ..
  56. ncbi request reprint Detection of plasminogen activators in oral cancer by laser capture microdissection combined with zymography
    Alejandro Curino
    Proteases and Tissue Remodeling Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Bethesda, MD 20892, USA
    Oral Oncol 40:1026-32. 2004
    ..In conclusion, LCM combined with zymography may be excellently suited for analyzing the prognostic significance and causal involvement of the plasminogen activation system in oral cancer...
  57. ncbi request reprint Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier function, hair follicle development, and thymic homeostasis
    Karin List
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Bethesda, Maryland, MD 20892, USA
    Oncogene 21:3765-79. 2002
    ..This study demonstrates that Matriptase/MT-SP1 has pleiotropic functions in the development of the epidermis, hair follicles, and cellular immune system...
  58. ncbi request reprint Collagen dissolution by keratinocytes requires cell surface plasminogen activation and matrix metalloproteinase activity
    Sarah Netzel-Arnett
    Matrix Metalloproteinase Unit, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 277:45154-61. 2002
    ..We propose that plasminogen activation facilitates keratinocyte-mediated collagen breakdown via the direct activation of matrix metalloproteinase-13 and possibly other fibrillar collagenases...
  59. ncbi request reprint Plasminogen promotes sarcoma growth and suppresses the accumulation of tumor-infiltrating macrophages
    Alejandro Curino
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Bethesda, Maryland, MD 20892, USA
    Oncogene 21:8830-42. 2002
    ..These data demonstrate that tumor cell-produced plasminogen activator and host plasminogen cooperate to facilitate soft tissue sarcoma growth and suppress the accumulation of tumor-infiltrating macrophages...
  60. pmc TMPRSS13 deficiency impairs stratum corneum formation and epidermal barrier acquisition
    Daniel H Madsen
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, U S A
    Biochem J 461:487-95. 2014
    ..The present study provides the first biological function for the transmembrane serine protease TMPRSS13. ..
  61. doi request reprint Mechanism of FGF23 processing in fibrous dysplasia
    Nisan Bhattacharyya
    Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    J Bone Miner Res 27:1132-41. 2012
    ..These data support the model wherein glycosylation by ppGalNAcT3 inhibits FGF23 cleavage by furin and suggest that FGF23 processing is a regulated process that controls overall FGF23 activity in FD patients...
  62. pmc Matriptase deletion initiates a Sjögren's syndrome-like disease in mice
    Hongen Yin
    Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 9:e82852. 2014
    ....
  63. ncbi request reprint Urokinase-type plasminogen activator stimulation of monocyte matrix metalloproteinase-1 production is mediated by plasmin-dependent signaling through annexin A2 and inhibited by inactive plasmin
    Yahong Zhang
    Immunopathology Section, National Institute of Dental and Craniofacial Research NIH, Bethesda, MD 20892, USA
    J Immunol 179:3297-304. 2007
    ..Furthermore, binding of inactive plasmin to annexin A2 inhibited plasmin induction of MMP-1, suggesting that inactive plasmin may be useful in suppressing inflammation...
  64. pmc The source of matrix-degrading enzymes in human cancer: Problems of research reproducibility and possible solutions
    Daniel H Madsen
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892
    J Cell Biol 209:195-8. 2015
    ..Our analysis of these studies identifies likely reasons as to why this may be the case, which has implications for the broader issue of research reproducibility. ..
  65. ncbi request reprint Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi's sarcomagenesis and can promote the tumorigenic potential of viral latent genes
    Silvia Montaner
    Cell Growth Regulation Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    Cancer Cell 3:23-36. 2003
    ..Endothelial cells expressing vGPCR were further able to promote tumor formation by cells expressing KSHV latent genes, suggestive of a cooperative role among viral genes in the promotion of Kaposi's sarcomagenesis...
  66. ncbi request reprint Potent inhibition of tumor angiogenesis by the matrix metalloproteinase-activated anthrax lethal toxin: implications for broad anti-tumor efficacy
    Randall W Alfano
    Cancer Research Institute of Scott and White Memorial Hospital, Temple, Texas 76502, USA
    Cell Cycle 7:745-9. 2008
    ..The MMP-activated LeTx showed potent angiogenic inhibition in vivo in the absence of systemic toxicity. Based on these studies, this attenuated toxin has clinical potential as a broad anti-tumor agent...
  67. pmc Cytotoxicity of the matrix metalloproteinase-activated anthrax lethal toxin is dependent on gelatinase expression and B-RAF status in human melanoma cells
    Randall W Alfano
    Scott and White Cancer Research Institute Memorial Hospital, 5701 South Airport Road, Temple, TX 76502, USA
    Mol Cancer Ther 7:1218-26. 2008
    ..This finding will aid in the better selection of patients that will potentially respond to MMP-activated LeTx therapy...
  68. ncbi request reprint Systematic urokinase-activated anthrax toxin therapy produces regressions of subcutaneous human non-small cell lung tumor in athymic nude mice
    Yunpeng Su
    Cancer Research Institute, Scott and White Memorial Hospital, Temple, Texas, USA
    Cancer Res 67:3329-36. 2007
    ..Complete histologic remission lasting 60 days occurred in 30% of animals. PrAgU2/FP59 showed dramatic anti-NSCLC efficacy and warrants further clinical development for therapy of patients with advanced NSCLC...
  69. pmc Hepatocyte growth factor activator inhibitor-1 has a complex subcellular itinerary
    Sine Godiksen
    Department of Cellular and Molecular Medicine, University of Copenhagen, The Panum Institute, Blegdamsvej 3, DK 2200 Copenhagen N, Denmark
    Biochem J 413:251-9. 2008
    ....
  70. ncbi request reprint A urokinase-activated recombinant anthrax toxin is selectively cytotoxic to many human tumor cell types
    Ralph J Abi-Habib
    Cancer Research Institute of Scott and White Memorial Hospital, Temple, Texas 76502, USA
    Mol Cancer Ther 5:2556-62. 2006
    ..Furthermore, we identify three molecular markers, anthrax toxin receptor, uPA, and uPA receptor, which can be used as predictors of tumor cell sensitivity to PrAgU2/FP59...
  71. ncbi request reprint Membrane anchored serine proteases: a rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer
    Sarah Netzel-Arnett
    Vascular Biology Department, Jerome H Holland Laboratory for the Biological Sciences, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855, USA
    Cancer Metastasis Rev 22:237-58. 2003
    ..Diagnostic or therapeutic targeting of the membrane anchored serine proteases has potential as promising new approaches for the treatment of cancer and other diseases...
  72. ncbi request reprint Antitumor efficacy of a urokinase activation-dependent anthrax toxin
    Birgitte Rønø
    Institute of Molecular Pathology, University of Copenhagen, Denmark
    Mol Cancer Ther 5:89-96. 2006
    ..Taken together, these data indicate that uPA-activated toxins may be promising candidates for targeted therapy of human cancers that overexpress uPA and its receptor...
  73. ncbi request reprint Evidence for a matriptase-prostasin proteolytic cascade regulating terminal epidermal differentiation
    Sarah Netzel-Arnett
    Center for Vascular and Inflammatory Diseases and Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
    J Biol Chem 281:32941-5. 2006
    ..These data suggest that matriptase, an autoactivating protease, acts upstream from prostasin to initiate a zymogen cascade that is essential for epidermal differentiation...
  74. ncbi request reprint Extracellular collagenases and the endocytic receptor, urokinase plasminogen activator receptor-associated protein/Endo180, cooperate in fibroblast-mediated collagen degradation
    Daniel H Madsen
    Finsen Laboratory, Rigshospitalet, Ole Maaløes Vej 5, DK 2200 Copenhagen N, Denmark
    J Biol Chem 282:27037-45. 2007
    ....
  75. ncbi request reprint Peptide toxins directed at the matrix dissolution systems of cancer cells
    Arthur E Frankel
    Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    Protein Pept Lett 9:1-14. 2002
    ..These recombinant fusion proteins provide a novel class of anti-cancer agents that will enter clinical trials in the next several years...
  76. ncbi request reprint Localization of regulatory elements mediating constitutive and cytokine-stimulated plasminogen gene expression
    Felizabel Garcia Bannach
    Department of Cell Biology, Division of Vascular Biology, Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 277:38579-88. 2002
    ..These results indicate the presence of regulatory elements in the 5'-flanking region of the murine plasminogen promoter that may regulate murine plasminogen gene expression and, hence, plasmin activity...
  77. ncbi request reprint Anthrax target in macrophages unveiled
    Thomas H Bugge
    Nat Genet 38:137-8. 2006
  78. ncbi request reprint Optical zymography for specific detection of urokinase plasminogen activator activity in biological samples
    Benedict Law
    Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Anal Biochem 338:151-8. 2005
    ..We were able to directly measure uPA activities in different cancer cell lines. This newly developed technique could be expanded to nearly all proteases, including the ones that cannot be analyzed by traditional zymography...
  79. ncbi request reprint Diphtheria toxin-murine granulocyte-macrophage colony-stimulating factor-induced hepatotoxicity is mediated by Kupffer cells
    Marlena M Westcott
    Department of Internal Medicine, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    Mol Cancer Ther 3:1681-9. 2004
    ..Furthermore, alternative fusion toxins with potentially reduced hepatotoxicity are presented...
  80. ncbi request reprint Hu/Mu ProtIn oligonucleotide microarray: dual-species array for profiling protease and protease inhibitor gene expression in tumors and their microenvironment
    Donald R Schwartz
    Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA
    Mol Cancer Res 5:443-54. 2007
    ....
  81. ncbi request reprint A urokinase-activated recombinant diphtheria toxin targeting the granulocyte-macrophage colony-stimulating factor receptor is selectively cytotoxic to human acute myeloid leukemia blasts
    Ralph J Abi-Habib
    Department of Biochemistry and Molecular Biology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    Blood 104:2143-8. 2004
    ..These results indicate that DTU2GMCSF may be a selective and potent agent for the treatment of patients with AML...
  82. ncbi request reprint Design, synthesis, and characterization of urokinase plasminogen-activator-sensitive near-infrared reporter
    Benedict Law
    Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Chem Biol 11:99-106. 2004
    ..No activation with negative control compounds and uPA inhibitors could be measured. These data indicate that the optimized preparation should be useful for imaging uPA in cancer...
  83. ncbi request reprint uPARAP/endo180 directs lysosomal delivery and degradation of collagen IV
    Lars Kjøller
    Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark
    Exp Cell Res 293:106-16. 2004
    ..A similar localization pattern was observed for collagen V, suggesting that uPARAP/endo180 might be generally involved in collagen degradation...
  84. ncbi request reprint The low density lipoprotein receptor-related protein modulates protease activity in the brain by mediating the cellular internalization of both neuroserpin and neuroserpin-tissue-type plasminogen activator complexes
    Alexandra Makarova
    Department of Vascular Biology, Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA
    J Biol Chem 278:50250-8. 2003
    ..In summary, neuroserpin levels appear to be carefully regulated by LRP and an unidentified cofactor, and this pathway may be critical for maintaining the balance between proteases and inhibitors...
  85. pmc MT1-matrix metalloproteinase directs arterial wall invasion and neointima formation by vascular smooth muscle cells
    Sergey Filippov
    Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan, Ann Arbor, 48109, USA
    J Exp Med 202:663-71. 2005
    ..These studies suggest that therapeutic interventions designed to target MT1-MMP could prove beneficial in a range of human vascular disease states associated with the destructive remodeling of the vessel wall extracellular matrix...