Hideyuki Saya

Summary

Affiliation: Keio University
Country: Japan

Publications

  1. ncbi request reprint Mechanism and biological significance of CD44 cleavage
    Osamu Nagano
    Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860 8556, Japan
    Cancer Sci 95:930-5. 2004
  2. ncbi request reprint Presenilin-dependent gamma-secretase activity mediates the intramembranous cleavage of CD44
    Daizo Murakami
    Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, Japan
    Oncogene 22:1511-6. 2003
  3. doi request reprint Fibroblast growth factor-2 is an important factor that maintains cellular immaturity and contributes to aggressiveness of osteosarcoma
    Takatsune Shimizu
    Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160 8582, Japan
    Mol Cancer Res 10:454-68. 2012
  4. ncbi request reprint [Role of CD44-mediated signal in cancer invasion and metastasis]
    Hideyuki Saya
    Tanpakushitsu Kakusan Koso 53:1225-30. 2008
  5. pmc Mad2 inhibits the mitotic kinesin MKlp2
    Sang Hyun Lee
    Program in Cancer and Stem Cell Biology, Graduate Medical School, Duke National University of Singapore, 169857 Singapore
    J Cell Biol 191:1069-77. 2010
  6. doi request reprint The cell cycle regulator Cdh1 controls the pool sizes of hematopoietic stem cells and mature lineage progenitors by protecting from genotoxic stress
    Jo Ishizawa
    Division of Gene Regulation, Institute for Advanced Medical Research, Department of Medicine, School of Medicine, Keio University, Tokyo, Japan
    Cancer Sci 102:967-74. 2011
  7. doi request reprint Transient depletion of p53 followed by transduction of c-Myc and K-Ras converts ovarian stem-like cells into tumor-initiating cells
    Takeshi Motohara
    Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku ku, Tokyo 160 8582, Japan
    Carcinogenesis 32:1597-606. 2011
  8. pmc Invasion precedes tumor mass formation in a malignant brain tumor model of genetically modified neural stem cells
    Oltea Sampetrean
    Division of Gene Regulation, School of Medicine, Keio University, Tokyo, Japan
    Neoplasia 13:784-91. 2011
  9. doi request reprint CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth
    Takatsugu Ishimoto
    Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku ku, Tokyo 160 8582, Japan
    Cancer Cell 19:387-400. 2011
  10. pmc Tumor necrosis factor-alpha regulates transforming growth factor-beta-dependent epithelial-mesenchymal transition by promoting hyaluronan-CD44-moesin interaction
    Eri Takahashi
    Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo 160 8582, Japan
    J Biol Chem 285:4060-73. 2010

Collaborators

Detail Information

Publications37

  1. ncbi request reprint Mechanism and biological significance of CD44 cleavage
    Osamu Nagano
    Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860 8556, Japan
    Cancer Sci 95:930-5. 2004
    ..An understanding of the underlying mechanism of these cleavages of CD44 could provide novel therapeutic targets for cancer cell invasion and metastasis...
  2. ncbi request reprint Presenilin-dependent gamma-secretase activity mediates the intramembranous cleavage of CD44
    Daizo Murakami
    Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, Japan
    Oncogene 22:1511-6. 2003
    ..Our present findings suggest important implications for understanding CD44-dependent signal transduction and a potential role of PS/gamma-secretase activity in the functional regulation of adhesion molecules...
  3. doi request reprint Fibroblast growth factor-2 is an important factor that maintains cellular immaturity and contributes to aggressiveness of osteosarcoma
    Takatsune Shimizu
    Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160 8582, Japan
    Mol Cancer Res 10:454-68. 2012
    ..The combined blockade of the signaling pathways of several growth factors, including Fgf2, might be useful in controlling the aggressiveness of osteosarcoma...
  4. ncbi request reprint [Role of CD44-mediated signal in cancer invasion and metastasis]
    Hideyuki Saya
    Tanpakushitsu Kakusan Koso 53:1225-30. 2008
  5. pmc Mad2 inhibits the mitotic kinesin MKlp2
    Sang Hyun Lee
    Program in Cancer and Stem Cell Biology, Graduate Medical School, Duke National University of Singapore, 169857 Singapore
    J Cell Biol 191:1069-77. 2010
    ..This correlates with an increased incidence of cytokinesis failure. Together, these findings reveal that MKlp2 is a novel mitotic target of Mad2 necessary for proper mitotic progression and cytokinesis...
  6. doi request reprint The cell cycle regulator Cdh1 controls the pool sizes of hematopoietic stem cells and mature lineage progenitors by protecting from genotoxic stress
    Jo Ishizawa
    Division of Gene Regulation, Institute for Advanced Medical Research, Department of Medicine, School of Medicine, Keio University, Tokyo, Japan
    Cancer Sci 102:967-74. 2011
    ..This is the first report revealing Cdh1 function in adult hematopoiesis and showing a role of Cdh1 in a G2/M checkpoint regulation in vivo...
  7. doi request reprint Transient depletion of p53 followed by transduction of c-Myc and K-Ras converts ovarian stem-like cells into tumor-initiating cells
    Takeshi Motohara
    Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku ku, Tokyo 160 8582, Japan
    Carcinogenesis 32:1597-606. 2011
    ..These data reveal a role for p53 in the development and expansion of ovarian stem-like tumor cells and subsequent malignant progression...
  8. pmc Invasion precedes tumor mass formation in a malignant brain tumor model of genetically modified neural stem cells
    Oltea Sampetrean
    Division of Gene Regulation, School of Medicine, Keio University, Tokyo, Japan
    Neoplasia 13:784-91. 2011
    ..Our results showed that perivascular and intraparenchymal tumor cell migration precede tumor mass formation in the adult brain, suggesting the need for an early and sustained anti-invasion therapy...
  9. doi request reprint CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth
    Takatsugu Ishimoto
    Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku ku, Tokyo 160 8582, Japan
    Cancer Cell 19:387-400. 2011
    ..It also induced activation of p38(MAPK), a downstream target of ROS, and expression of the gene for the cell cycle inhibitor p21(CIP1/WAF1). These findings establish a function for CD44v in regulation of ROS defense and tumor growth...
  10. pmc Tumor necrosis factor-alpha regulates transforming growth factor-beta-dependent epithelial-mesenchymal transition by promoting hyaluronan-CD44-moesin interaction
    Eri Takahashi
    Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo 160 8582, Japan
    J Biol Chem 285:4060-73. 2010
    ..The production of hyaluronan and its interaction with CD44, thus, play an essential role in TNF-alpha-induced EMT and are potential therapeutic targets in fibrotic disorders...
  11. pmc Establishment of a choriocarcinoma model from immortalized normal extravillous trophoblast cells transduced with HRASV12
    Yusuke Kobayashi
    Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University and the Core Research for Evolutional Science and Technology CREST, Japan Science and Technology Agency, Tokyo, Japan
    Am J Pathol 179:1471-82. 2011
    ..Our murine model represents a potent new tool for studying the pathogenesis and treatment of choriocarcinoma...
  12. pmc The anaphase-promoting complex/cyclosome activator Cdh1 modulates Rho GTPase by targeting p190 RhoGAP for degradation
    Hideaki Naoe
    Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160 8582, Japan
    Mol Cell Biol 30:3994-4005. 2010
    ..Our data revealed a novel function for Cdh1 as a regulator of Rho and provided insights into the role of Cdh1 in cell cytoskeleton organization and cell motility...
  13. doi request reprint Molecular mechanisms regulating dissociation of cell-cell junction of epithelial cells by oxidative stress
    Junko Inumaru
    Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160 8582, Japan
    Genes Cells 14:703-16. 2009
    ..These findings suggest that oxidative stress is a crucial factor to induce the cell-cell dissociation, an initial step of EMT, but does not provide sufficient signals to establish and to maintain the EMT...
  14. doi request reprint [Encounter of cancer cells with bone. The significance of cancer stem cells and epithelial-mesenchymal transition in tumor invasion and metastasis]
    Go J Yoshida
    Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine
    Clin Calcium 21:411-7. 2011
    ..However, some recent studies suggest that EMT is not essential requirement for tumor invasion and metastasis. Herein, we discuss the biological significance of CSCs and EMT in tumor invasion and metastasis...
  15. pmc Induction of ZEB proteins by inactivation of RB protein is key determinant of mesenchymal phenotype of breast cancer
    Yoshimi Arima
    Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo 160 8582, Japan
    J Biol Chem 287:7896-906. 2012
    ..Together, our findings suggest that RB inactivation contributes to tumor progression not only through loss of cell cycle control but also through up-regulation of ZEB expression and induction of an invasive phenotype...
  16. doi request reprint CD44+ slow-cycling tumor cell expansion is triggered by cooperative actions of Wnt and prostaglandin E2 in gastric tumorigenesis
    Takatsugu Ishimoto
    Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan
    Cancer Sci 101:673-8. 2010
    ..These observations suggest that PGE(2)-mediated inflammatory signaling and Wnt signaling cooperatively trigger the expansion of CD44(+) slow-cycling stem-like cells in SCJ, leading to development of lethal gastric tumors in mice...
  17. doi request reprint Loss of p16 expression is associated with the stem cell characteristics of surface markers and therapeutic resistance in estrogen receptor-negative breast cancer
    Yoshimi Arima
    Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo 160 8582, Japan
    Int J Cancer 130:2568-79. 2012
    ..Consistent with this conclusion, immunohistochemical analysis of the clinical samples suggests that low p16 expression in TNBC is associated with resistance to preoperative chemotherapy...
  18. doi request reprint Decreased expression of neurofibromin contributes to epithelial-mesenchymal transition in neurofibromatosis type 1
    Yoshimi Arima
    Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan
    Exp Dermatol 19:e136-41. 2010
    ..Our findings suggest that the loss of neurofibromin activated the EMT-related signaling pathway and that the excessive mesenchymal reaction may play a key role in the development of NF1-associated neurofibromas...
  19. doi request reprint Maintenance of HCT116 colon cancer cell line conforms to a stochastic model but not a cancer stem cell model
    Kazuharu Kai
    Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan
    Cancer Sci 100:2275-82. 2009
    ..Thus, HCT116 cells have plasticity when they are set in floating-spheres, suggesting that maintenance of the HCT116 cell line conforms to a stochastic model, not a CSC model...
  20. pmc Functional analysis of HOXD9 in human gliomas and glioma cancer stem cells
    Masanao Tabuse
    Neuroimmunology Research Group, Keio University School of Medicine, 35 Shinanomachi, Shinjuku ku, Tokyo 160 8582, Japan
    Mol Cancer 10:60. 2011
    ..HOX genes encode a family of homeodomain-containing transcription factors involved in the determination of cell fate and identity during embryonic development. They also behave as oncogenes in some malignancies...
  21. ncbi request reprint [Molecular mechanism regulating effect of anti-cancer agents]
    Hideyuki Saya
    Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Japan
    Gan To Kagaku Ryoho 36:1-5. 2009
    ..Given that G1 and G2 checkpoint functions are generally impaired in cancer cells, cells with DNA damage are unable to maintain G2 arrest and eventually die as they enter mitosis. This process is known as mitotic catastrophe...
  22. doi request reprint Breast cancer stem cells
    Kazuharu Kai
    Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Keio University, 35 Shinano machi, Shinjuku ku, Tokyo 160 8582, Japan
    Breast Cancer 17:80-5. 2010
    ..The emerging picture of the biological properties of BCSCs would contribute for devising innovative therapies for breast cancer, targeting the intrinsic and extrinsic factors that maintain the BCSCs...
  23. ncbi request reprint [Current clinical trials using new targeted therapies for myeloid leukemia and the research trends]
    Jo Ishizawa
    Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine
    Nihon Rinsho 67:1932-7. 2009
    ..This review summarizes the current clinical trials using new targeted therapies and research trends on myeloid leukemia...
  24. pmc RNA-binding protein Musashi1 modulates glioma cell growth through the post-transcriptional regulation of Notch and PI3 kinase/Akt signaling pathways
    Jun Muto
    Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan
    PLoS ONE 7:e33431. 2012
    ..These results suggest that MSI1 increases the growth and/or survival of certain types of glioma cells by promoting the activation of both Notch and PI(3) kinase/Akt signaling...
  25. ncbi request reprint [Molecular mechanism of cell death induced by chemotherapeutic agents]
    Hideyuki Saya
    Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinano machi, Shinjuku ku, Tokyo 160 8582, Japan
    Brain Nerve 61:843-7. 2009
    ..An understanding of the molecular mechanisms of chemotherapy will enable us to use conventional drugs more appropriately for cancer treatment...
  26. pmc M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis
    Yoshiaki Kubota
    Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Shinjuku ku, Tokyo 160 8582, Japan
    J Exp Med 206:1089-102. 2009
    ..Continuous M-CSF inhibition did not affect healthy vascular and lymphatic systems outside tumors. These results suggest that M-CSF-targeted therapy is an ideal strategy for treating ocular neovascular diseases and cancer...
  27. doi request reprint Involvement of hyaluronan and its receptor CD44 with choroidal neovascularization
    Hiroshi Mochimaru
    Department of Ophthalmology, Laboratory of Retinal Cell Biology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan
    Invest Ophthalmol Vis Sci 50:4410-5. 2009
    ..The purpose of the present study was to clarify a role of HA and CD44 in the development of choroidal neovascularization (CNV)...
  28. ncbi request reprint [Molecular mechanisms of brain tumor invasion]
    Hideyuki Saya
    Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University
    Nihon Rinsho 63:61-7. 2005
  29. pmc Cell-matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca(2+) influx and PKC activation
    Osamu Nagano
    Dept of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, 1 1 1 Honjo, Kumamoto 860 8556, Japan
    J Cell Biol 165:893-902. 2004
    ..The spatio-temporal regulation of two independent signaling pathways for CD44 cleavage plays a crucial role in cell-matrix interaction and cell migration...
  30. ncbi request reprint Aurora-A - a guardian of poles
    Tomotoshi Marumoto
    Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, 1 1 1 Honjo, Kumamoto 860 8556, Japan
    Nat Rev Cancer 5:42-50. 2005
    ..What are the normal physiological roles of Aurora-A, how are these regulated and how might the enzyme function during tumorigenesis?..
  31. ncbi request reprint Hyaluronan oligosaccharides induce CD44 cleavage and promote cell migration in CD44-expressing tumor cells
    Kazuki N Sugahara
    Laboratory of Molecular and Cellular Recognition, Osaka University Graduate School of Medicine, 2 2, Yamada oka, Suita 565 0871, Japan
    J Biol Chem 278:32259-65. 2003
    ..These results raise the possibility that small HA oligosaccharides, which are known to occur in various tumor tissues, promote tumor invasion by enhancing the tumor cell motility that may be driven by CD44 cleavage...
  32. ncbi request reprint ADAM-17 associated with CD44 cleavage and metastasis in oral squamous cell carcinoma
    Yasuo Takamune
    Department of Oral and Maxillofacial Surgery, Graduate School of Medical Sciences, Kumamoto University, 1 1 1 Honjo, Kumamoto 860 8556, Japan
    Virchows Arch 450:169-77. 2007
    ..The level of ADAM-17 expression was significantly correlated to the nodal metastasis and local recurrence in oral SCC. Our findings suggest that ADAM-17 is involved in CD44 cleavage and contributes to tumor progression in oral SCC...
  33. ncbi request reprint [Aurora kinases: Functions and roles in tumorigenesis]
    Hideyuki Saya
    Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, 1 1 1 Honjo, Kumamoto 860 8556, Japan
    Seikagaku 79:131-9. 2007
  34. ncbi request reprint The UHRF family: oncogenes that are drugable targets for cancer therapy in the near future?
    Christian Bronner
    CNRS UMR 7175, Département de Pharmacologie et Pharmacochimie des Interactions Moléculaires et Cellulaires, Faculte de Pharmacie, 74 route du Rhin, BP 60024, 67401, Illkirch Cedex, France
    Pharmacol Ther 115:419-34. 2007
    ..Alteration of these regulatory mechanisms, such as those occurring in cancer cells, may be involved in carcinogenesis. The reasons why the UHRF family could be an interesting target for developing anticancer drugs is also developed...
  35. doi request reprint EGFR and ErbB2 are functionally coupled to CD44 and regulate shedding, internalization and motogenic effect of CD44
    Zsuzsanna Pályi-Krekk
    Department of Biophysics and Cell Biology, Medical and Health Science Center, University of Debrecen, 1 Egyetem Square, H 4010 Debrecen, Hungary
    Cancer Lett 263:231-42. 2008
    ..Our experiments point to an unexpected, but potentially important mechanism of action of ErbB receptor-targeted monoclonal antibodies used in the treatment of cancer...
  36. doi request reprint Rb depletion results in deregulation of E-cadherin and induction of cellular phenotypic changes that are characteristic of the epithelial-to-mesenchymal transition
    Yoshimi Arima
    Radiobiology Division, National Cancer Center Research Institute, Tokyo 104 0045, Japan
    Cancer Res 68:5104-12. 2008
    ....
  37. pmc Proteolytic cleavage of the CD44 adhesion molecule in multiple human tumors
    Isamu Okamoto
    Department of Microbiology and Immunology, Kimmel Cancer Institute, BLSB 2002, Thomas Jefferson University, 233 S 10th St, Philadelphia, PA 19107, USA
    Am J Pathol 160:441-7. 2002
    ..Tumors expressing a CD44 splice variant showed a significantly higher incidence of enhanced CD44 cleavage. The wide prevalence of CD44 cleavage suggests that it plays an important role in the pathogenesis of human tumors...