Functions of Autocrine Motility Factor at the Tumor Microenvironment

  • Tatsuyoshi Funasaka
  • Avraham Raz
Part of the TTME book series (TTME, volume 2)

Autocrine motility factor (AMF) is a tumor-secreted cytokine and is abundant at tumor sites, where it may affect the process of tumor growth and metastasis. AMF is a multifunctional protein capable of affecting cell migration, invasion, proliferation, and survival, and possesses phosphoglucose isomerase activity and can catalyze the step in glycolysis and gluconeogenesis. Here, we review the role of AMF and tumor environment on malignant processes. The outcome of metastasis depends on multiple interactions between tumor cells and homeostatic mechanisms; therefore elucidation of the tumor/host interactions in the tumor microenvironment is essential in the development of new prevention and treatment strategies. Such knowledge might provide clues to develop new future therapeutic approaches for human cancers.


Motility factor Autocrine effect Survival Apoptosis Tumor-host interaction Extracellular matrix Collagen Cytokines 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Fidler IJ, Poste G: The cellular heterogeneity of malignant neoplasms: implications for adjuvant chemotherapy. Semin Oncol 12: 207–221, 1985PubMedGoogle Scholar
  2. 2.
    Schnipper L: Clinical implications of tumor-cell heterogeneity. N Engl J Med 314: 1423–1431, 1986PubMedGoogle Scholar
  3. 3.
    Liotta LA, Thorgeirsson UP, Garbisa S: Role of collagenases in tumor cell invasion. Cancer Metastasis Rev 1: 277–288, 1982CrossRefPubMedGoogle Scholar
  4. 4.
    Strauli P, Haemmerli G: The role of cancer cell motility in invasion. Cancer Metastasis Rev 3: 127–141, 1984CrossRefPubMedGoogle Scholar
  5. 5.
    Woolley DE: Collagenolytic mechanisms in tumor cell invasion. Cancer Metastasis Rev 3: 361–372, 1984CrossRefPubMedGoogle Scholar
  6. 6.
    Erickson CA: Cell migration in the embryo and adult organism. Curr Opin Cell Biol 2: 67–74, 1990CrossRefPubMedGoogle Scholar
  7. 7.
    Lauffenburger DA, Horwitz AF: Cell migration: a physically integrated molecular process. Cell 84: 359–369, 1996CrossRefPubMedGoogle Scholar
  8. 8.
    Carr I: Lymphatic metastasis. Cancer Metastasis Rev 2: 307–317, 1983CrossRefPubMedGoogle Scholar
  9. 9.
    Carr J, Dreher B, Carr I: Lymphatic metastasis; lymphangiochemotherapy of mammary cancer: ascitic form of rat mammary adenocarcinoma 13762. Clin Exp Metastasis 1: 29–38, 1983CrossRefPubMedGoogle Scholar
  10. 10.
    Bouwens L, Jacobs R, Remels L, Wisse E: Natural cytotoxicity of rat hepatic natural killer cells and macrophages against a syngeneic colon adenocarcinoma. Cancer Immunol Immunother 27: 137–141, 1988CrossRefPubMedGoogle Scholar
  11. 11.
    Weiss L, Orr FW, Honn KV: Interactions between cancer cells and the microvasculature: a rate-regulator for metastasis. Clin Exp Metastasis 7: 127–167, 1989CrossRefPubMedGoogle Scholar
  12. 12.
    Crissman JD, Hatfield J, Schaldenbrand M, Sloane BF, Honn KV: Arrest and extravasation of B16 amelanotic melanoma in murine lungs: a light and electron microscopic study. Lab Invest 53: 470–478, 1985PubMedGoogle Scholar
  13. 13.
    Folkman J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1: 27–31, 1995CrossRefPubMedGoogle Scholar
  14. 14.
    Weidner N: Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol 147: 9–19, 1995PubMedGoogle Scholar
  15. 15.
    Stoker M, Gherardi E: Regulation of cell movement: the motogenic cytokines. Biochim Biophys Acta 1072: 81–102, 1991PubMedGoogle Scholar
  16. 16.
    Lazar-Molnar E, Hegyesi H, Toth S, Falus A: Autocrine and paracrine regulation by cytokines and growth factors in melanoma. Cytokine 12: 547–554, 2000CrossRefPubMedGoogle Scholar
  17. 17.
    Baggetto LG: Biochemical, genetic, and metabolic adaptations of tumor cells that express the typical multidrug-resistance phenotype: reversion by new therapies. J Bioenerg Biomembr 29: 401–413, 1997CrossRefPubMedGoogle Scholar
  18. 18.
    Kerbel RS: Growth dominance of the metastatic cancer cell: cellular and molecular aspects. Adv Cancer Res 55: 87–132, 1990CrossRefPubMedGoogle Scholar
  19. 19.
    Singh RK, Bucana CD, Gutman M, Fan D, Wilson MR, Fidler IJ: Organ site-dependent expression of basic fibroblast growth factor in human renal cell carcinoma cells. Am J Pathol 145: 365–374, 1994PubMedGoogle Scholar
  20. 20.
    Liotta LA, Kohn EC: The microenvironment of the tumour-host interface. Nature 411: 375–379, 2001CrossRefPubMedGoogle Scholar
  21. 21.
    Fidler IJ: The organ microenvironment and cancer metastasis. Differentiation 70: 498–505, 2002CrossRefPubMedGoogle Scholar
  22. 22.
    Paget S: The distribution of secondary growths in cancer of the breast. Lancet 1: 571–573, 1889CrossRefGoogle Scholar
  23. 23.
    Fidler IJ, Ellis LM: Neoplastic angiogenesis–not all blood vessels are created equal. N Engl J Med 351: 215–216, 2004CrossRefPubMedGoogle Scholar
  24. 24.
    Liotta LA, Tryggvason K, Garbisa S, Hart I, Foltz CM, Shafie S: Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature 284: 67–68, 1980CrossRefPubMedGoogle Scholar
  25. 25.
    Nakajima M, Morikawa K, Fabra A, Bucana CD, Fidler IJ: Influence of organ environment on extracellular matrix degradative activity and metastasis of human colon carcinoma cells. J Natl Cancer Inst 82: 1890–1898, 1990CrossRefPubMedGoogle Scholar
  26. 26.
    Gutman M, Singh RK, Xie K, Bucana CD, Fidler IJ: Regulation of interleukin-8 expression in human melanoma cells by the organ environment. Cancer Res 55: 2470–2475, 1995PubMedGoogle Scholar
  27. 27.
    Aaronson SA: Growth factors and cancer. Science 254: 1146–1153, 1991CrossRefPubMedGoogle Scholar
  28. 28.
    McCormick BA, Zetter BR: Interactions in angiogenesis and metastasis. Pharmacol Ther 53: 239–260, 1992CrossRefPubMedGoogle Scholar
  29. 29.
    Rodeck U, Melber K, Kath R, Menssen HD, Varello M, Atkinson B, Herlyn M: Constitutive expression of multiple growth factor genes by melanoma cells but not normal melanocytes. J Invest Dermatol 97: 20–26, 1991CrossRefPubMedGoogle Scholar
  30. 30.
    Nicolson GL: Cancer progression and growth: relationship of paracrine and autocrine growth mechanisms to organ preference of metastasis. Exp Cell Res 204: 171–180, 1993CrossRefPubMedGoogle Scholar
  31. 31.
    Radinsky R: Paracrine growth regulation of human colon carcinoma organ-specific metastasis. Cancer Metastasis Rev 12: 345–361, 1993CrossRefPubMedGoogle Scholar
  32. 32.
    Wilson J, Balkwill F: The role of cytokines in the epithelial cancer microenvironment. Semin Cancer Biol 12: 113–120, 2002CrossRefPubMedGoogle Scholar
  33. 33.
    Liotta LA, Mandler R, Murano G, Katz DA, Gordon RK, Chiang PK, Schiffmann E: Tumor cell autocrine motility factor. Proc Natl Acad Sci USA 83: 3302–3306, 1986CrossRefPubMedGoogle Scholar
  34. 34.
    Liotta LA, Rao CN, Barsky SH: Tumor invasion and the extracellular matrix. Lab Invest 49: 636–649, 1983PubMedGoogle Scholar
  35. 35.
    Turley EA: Molecular mechanisms of cell motility. Cancer Metastasis Rev 11: 1–3, 1992CrossRefPubMedGoogle Scholar
  36. 36.
    Seiki M: The cell surface: the stage for matrix metalloproteinase regulation of migration. Curr Opin Cell Biol 14: 624–632, 2002CrossRefPubMedGoogle Scholar
  37. 37.
    Gomm SA, Keevil BG, Thatcher N, Hasleton PS, Swindell RS: The value of tumour markers in lung cancer. Br J Cancer 58: 797–804, 1988PubMedGoogle Scholar
  38. 38.
    Baumann M, Kappl A, Lang T, Brand K, Siegfried W, Paterok E: The diagnostic validity of the serum tumor marker phosphohexose isomerase (PHI) in patients with gastrointestinal, kidney, and breast cancer. Cancer Invest 8: 351–356, 1990CrossRefPubMedGoogle Scholar
  39. 39.
    Filella X, Molina R, Jo J, Mas E, Ballesta AM: Serum phosphohexose isomerase activities in patients with colorectal cancer. Tumour Biol 12: 360–367, 1991PubMedGoogle Scholar
  40. 40.
    Tsutsumi S, Hogan V, Nabi IR, Raz A: Overexpression of the autocrine motility factor/phosphoglucose isomerase induces transformation and survival of NIH-3T3 fibroblasts. Cancer Res 63: 242–249, 2003PubMedGoogle Scholar
  41. 41.
    Yanagawa T, Watanabe H, Takeuchi T, Fujimoto S, Kurihara H, Takagishi K: Overexpression of autocrine motility factor in metastatic tumor cells: possible association with augmented expression of KIF3A and GDI-β. Lab Invest 84: 513–522, 2004CrossRefPubMedGoogle Scholar
  42. 42.
    Watanabe H, Takehana K, Date M, Shinozaki T, Raz, A: Tumor cell autocrine motility factor is the neuroleukin/phosphohexose isomerase polypeptide. Cancer Res 56: 2960–2963, 1996PubMedGoogle Scholar
  43. 43.
    Kim JW, Dang CV: Multifaceted roles of glycolytic enzymes. Trends Biochem Sci 30: 142–150, 2005CrossRefPubMedGoogle Scholar
  44. 44.
    Beutler E, West C, Britton HA, Harris J, Forman L: Glucosephosphate isomerase (GPI) deficiency mutations associated with hereditary nonspherocytic hemolytic anemia (HNSHA). Blood Cells Mol Dis 23: 402–409, 1997CrossRefPubMedGoogle Scholar
  45. 45.
    Jeffery CJ, Bahnson BJ, Chien W, Ringe D, Petsko GA: Crystal structure of rabbit phosphoglucose isomerase, a glycolytic enzyme that moonlights as neuroleukin, autocrin motility factor, and differentiation mediator. Biochemistry 39: 955–964, 2000CrossRefPubMedGoogle Scholar
  46. 46.
    Ravindranath Y, Paglia DE, Warrier I, Valentine W, Nakatani M, Brockway RA: Glucose phosphate isomerase deficiency as a cause of hydrops fetalis. N Engl J Med 316: 258–261, 1987PubMedGoogle Scholar
  47. 47.
    Matsumoto I, Staub A, Benoist C, Mathis D: Arthritis provoked by linked T and B cell recognition of a glycolytic enzyme. Science 286: 1732–1735, 1999CrossRefPubMedGoogle Scholar
  48. 48.
    Funasaka T, Haga A, Raz A, Nagase H: Tumor autocrine motility factor is an angiogenic factor that stimulates endothelial cell motility. Biochem Biophys Res Commun 285: 118–128, 2001CrossRefPubMedGoogle Scholar
  49. 49.
    Dang CV, Semenza GL: Oncogenic alterations of metabolism. Trends Biochem Sci 24: 68–72, 1999CrossRefPubMedGoogle Scholar
  50. 50.
    Gurney ME, Apatoff BR, Spear GT, Baumel MJ, Antel JP, Bania MB, Reder AT: Neuroleukin: a lymphokine product of lectin-stimulated T cells. Science 234: 574–581, 1986CrossRefPubMedGoogle Scholar
  51. 51.
    Xu W, Seiter K, Feldman E, Ahmed T, Chiao JW: The differentiation and maturation mediator for human myeloid leukemia cells shares homology with neuroleukin or phosphoglucose isomerase. Blood 87: 4502–4506, 1996PubMedGoogle Scholar
  52. 52.
    Yakirevich E, Naot Y: Cloning of a glucose phosphate isomerase/neuroleukin-like sperm antigen involved in sperm agglutination. Biol Reprod 62: 1016–1023, 2000CrossRefPubMedGoogle Scholar
  53. 53.
    Cao MJ, Osatomi K, Matsuda R, Ohkubo M, Hara K, Ishihara T: Purification of a novel serine proteinase inhibitor from the skeletal muscle of white croaker (Argyrosomus argentatus). Biochem Biophys Res Commun 272: 485–489, 2000CrossRefPubMedGoogle Scholar
  54. 54.
    Niinaka Y, Paku S, Haga A, Watanabe H, Raz A: Expression and secretion of neuroleukin/phosphohexose isomerase/maturation factor as autocrine motility factor by tumor cells. Cancer Res 58: 2667–2674, 1998PubMedGoogle Scholar
  55. 55.
    Silletti S, Watanabe H, Hogan V, Nabi IR, Raz A: Purification of B16-F1 melanoma autocrine motility factor and its receptor. Cancer Res 51: 3507–3511, 1991PubMedGoogle Scholar
  56. 56.
    Shimizu K, Tani M, Watanabe H, Nagamachi Y, Niinaka Y, Shiroishi T, Ohwada S, Raz A, Yokota J: The autocrine motility factor receptor gene encodes a novel type of seven transmembrane protein. FEBS Lett 456: 295–300, 1999CrossRefPubMedGoogle Scholar
  57. 57.
    Nabi IR, Watanabe H, Raz A: Autocrine motility factor and its receptor: role in cell locomotion and metastasis. Cancer Metastasis Rev 11: 5–20, 1992CrossRefPubMedGoogle Scholar
  58. 58.
    Silletti S, Raz A: Regulation of autocrine motility factor receptor expression in tumor cell locomotion and metastasis. Curr Top Microbiol Immunol 213: 137–169, 1996PubMedGoogle Scholar
  59. 59.
    Ohta Y, Minato H, Tanaka Y, Go T, Oda M, Watanabe Y: Autocrine motility factor receptor expression associates with tumor progression in thymoma. Int J Oncol 17: 259–264, 2000PubMedGoogle Scholar
  60. 60.
    Takanami I, Takeuchi K, Watanabe H, Yanagawa T, Takagishi K, Raz A: Significance of autocrine motility factor receptor gene expression as a prognostic factor in non-small-cell lung cancer. Int J Cancer 95: 384–387, 2001CrossRefPubMedGoogle Scholar
  61. 61.
    Timar J, Raso E, Dome B, Ladanyi A, Banfalvi T, Gilde K, Raz A: Expression and function of the AMF receptor by human melanoma in experimental and clinical systems. Clin Exp Metastasis 19: 225–232, 2002CrossRefPubMedGoogle Scholar
  62. 62.
    Folkman J, Klagsbrun M: Angiogenic factors. Science 235: 442–447, 1987CrossRefPubMedGoogle Scholar
  63. 63.
    Risau W, Sariola H, Zerwes HG, Sasse J, Ekblom P, Kemler R, Doetschman T: Vasculogenesis and angiogenesis in embryonic-stem-cell-derived embryoid bodies. Development 102: 471–478, 1988PubMedGoogle Scholar
  64. 64.
    Folkman J, Shing Y: Angiogenesis. J Biol Chem 267: 10931–10934, 1992PubMedGoogle Scholar
  65. 65.
    Liekens S, De Clercq E, Neyts J: Angiogenesis: regulators and clinical applications. Biochem Pharmacol 61: 253–270, 2001CrossRefPubMedGoogle Scholar
  66. 66.
    Zetter BR: Angiogenesis and tumor metastasis. Annu Rev Med 49: 407–424, 1998CrossRefPubMedGoogle Scholar
  67. 67.
    Weidner N, Folkman J, Pozza F, Bevilacqua P, Allred EN, Moore DH, Meli S, Gasparini G: Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst 84: 1875–1887, 1992CrossRefPubMedGoogle Scholar
  68. 68.
    Vermeulen PB, Gasparini G, Fox SB, Colpaert C, Marson LP, Gion M, Belien JA, de Waal RM, Van Marck E, Magnani E, Weidner N, Harris AL, Dirix LY: Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. Eur J Cancer 38: 1564–1579, 2002CrossRefPubMedGoogle Scholar
  69. 69.
    Shibuya M: Role of VEGF-flt receptor system in normal and tumor angiogenesis. Adv Cancer Res 67: 281–316, 1995CrossRefPubMedGoogle Scholar
  70. 70.
    Ferrara N: VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer 2: 795–803, 2002CrossRefPubMedGoogle Scholar
  71. 71.
    Hanahan D, Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86: 353–364, 1996CrossRefPubMedGoogle Scholar
  72. 72.
    Passaniti A, Taylor RM, Pili R, Guo Y, Long PV, Haney JA, Pauly RR, Grant DS, Martin GR: A simple, quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor. Lab Invest 67: 519–528, 1992PubMedGoogle Scholar
  73. 73.
    Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF: Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219: 983–985, 1983CrossRefPubMedGoogle Scholar
  74. 74.
    Connolly DT: Vascular permeability factor: a unique regulator of blood vessel function. J Cell Biochem 47: 219–223, 1991CrossRefPubMedGoogle Scholar
  75. 75.
    Nagy JA, Masse EM, Herzberg KT, Meyers MS, Yeo KT, Yeo TK, Sioussat TM, Dvorak HF: Pathogenesis of ascites tumor growth: vascular permeability factor, vascular hyperpermeability, and ascites fluid accumulation. Cancer Res 55: 360–368, 1995PubMedGoogle Scholar
  76. 76.
    de Vries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT: The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 255: 989–991, 1992CrossRefPubMedGoogle Scholar
  77. 77.
    Millauer B, Wizigmann-Voos S, Schnurch H, Martinez R, Moller NP, Risau W, Ullrich A: High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72: 835–846, 1993CrossRefPubMedGoogle Scholar
  78. 78.
    Plate KH, Breier G, Weich HA, Risau W: Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 359: 845–848, 1992CrossRefPubMedGoogle Scholar
  79. 79.
    Hatva E, Kaipainen A, Mentula P, Jaaskelainen J, Paetau A, Haltia M, Alitalo K: Expression of endothelial cell-specific receptor tyrosine kinases and growth factors in human brain tumors. Am J Pathol 146: 368–378, 1995PubMedGoogle Scholar
  80. 80.
    Warren RS, Yuan H, Matli MR, Gillett NA, Ferrara N: Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis. J Clin Invest 95: 1789–1797, 1995CrossRefPubMedGoogle Scholar
  81. 81.
    Funasaka T, Haga A, Raz A, Nagase H: Autocrine motility factor secreted by tumor cells upregulates vascular endothelial growth factor receptor (Flt-1) expression in endothelial cells. Int J Cancer 101: 217–223, 2002CrossRefPubMedGoogle Scholar
  82. 82.
    Kanno S, Oda N, Abe M, Terai Y, Ito M, Shitara K, Tabayashi K, Shibuya M, Sato Y: Roles of two VEGF receptors, Flt-1 and KDR, in the signal transduction of VEGF effects in human vascular endothelial cells. Oncogene 19: 2138–2146, 2000CrossRefPubMedGoogle Scholar
  83. 83.
    Soker S, Kaefer M, Johnson M, Klagsbrun M, Atala A, Freeman MR: Vascular endothelial growth factor-mediated autocrine stimulation of prostate tumor cells coincides with progression to a malignant phenotype. Am J Pathol 159: 651–659, 2001PubMedGoogle Scholar
  84. 84.
    Barleon B, Siemeister G, Martiny-Baron G, Weindel K, Herzog C, Marme D: Vascular endothelial growth factor up-regulates its receptor fms-like tyrosine kinase 1 (FLT-1) and a soluble variant of FLT-1 in human vascular endothelial cells. Cancer Res 57: 5421–5425, 1997PubMedGoogle Scholar
  85. 85.
    Semenza GL: HIF-1 and human disease: one highly involved factor. Genes Dev 14: 1983–1991, 2000PubMedGoogle Scholar
  86. 86.
    Harris AL: Hypoxia – a key regulatory factor in tumour growth. Nat Rev Cancer 2: 38–47, 2002CrossRefPubMedGoogle Scholar
  87. 87.
    Semenza GL: Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3: 721–732, 2003CrossRefPubMedGoogle Scholar
  88. 88.
    Wang GL, Jiang BH, Rue EA, Semenza GL: Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA 92: 5510–5514, 1995CrossRefPubMedGoogle Scholar
  89. 89.
    Huang LE, Gu J, Schau M, Bunn HF: Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent degradation domain via the ubiquitinproteasome pathway. Proc Natl Acad Sci USA 95: 7987–7992, 1998CrossRefPubMedGoogle Scholar
  90. 90.
    Kallio PJ, Wilson WJ, O’Brien S, Makino Y, Poellinger L: Regulation of the hypoxia-inducible transcription factor 1alpha by the ubiquitin-proteasome pathway. J Biol Chem 274: 6519–6525, 1999CrossRefPubMedGoogle Scholar
  91. 91.
    Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, Wykoff CC, Pugh CW, Maher ER, Ratcliffe PJ: The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399: 271–275, 1999CrossRefPubMedGoogle Scholar
  92. 92.
    Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG Jr: HIF-1alpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 292: 464–468, 2001CrossRefPubMedGoogle Scholar
  93. 93.
    Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, Kriegsheim Av, Hebestreit HF, Mukherji M, Schofiels CJ, Maxwell PH, Pugh CW, Ratcliffe PJ: Targeting of HIF-1alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292: 468–472, 2001CrossRefPubMedGoogle Scholar
  94. 94.
    Sivitz WI, Lund DD, Yorek B, Grover-McKay M, Schmid PG: Pretranslational regulation of two cardiac glucose transporters in rats exposed to hypobaric hypoxia. Am J Physiol 263: E562–E569, 1992PubMedGoogle Scholar
  95. 95.
    Semenza GL, Roth PH, Fang HM, Wang GL: Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J Biol Chem 269: 23757–23763, 1994PubMedGoogle Scholar
  96. 96.
    Daly EB, Wind T, Jiang XM, Sun L, Hogg PJ: Secretion of phosphoglycerate kinase from tumour cells is controlled by oxygen-sensing hydroxylases. Biochim Biophys Acta 1691: 17–22, 2004CrossRefPubMedGoogle Scholar
  97. 97.
    Yoon DY, Buchler P, Saarikoski ST, Hines OJ, Reber HA, Hankinson O: Identification of genes differentially induced by hypoxia in pancreatic cancer cells. Biochem Biophys Res Commun 288: 882–886, 2001CrossRefPubMedGoogle Scholar
  98. 98.
    Niizeki H, Kobayashi M, Horiuchi I, Akakura N, Chen J, Wang J, Hamada JI, Seth P, Katoh H, Watanabe H, Raz A, Hosokawa M: Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells. Br J Cancer 86: 1914–1919, 2002CrossRefPubMedGoogle Scholar
  99. 99.
    Krishnamachary B, Berg-Dixon S, Kelly B, Agani F, Feldser D, Ferreira G, Iyer N, LaRusch J, Pak B, Taghavi P, Semenza GL: Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Res 63: 1138–1143, 2003PubMedGoogle Scholar
  100. 100.
    Funasaka T, Yanagawa T, Hogan V, Raz A: Regulation of phosphoglucose isomerase/autocrine motility factor expression by hypoxia. FASEB J 19: 1422–1430, 2005CrossRefPubMedGoogle Scholar
  101. 101.
    Haga A, Funasaka T, Niinaka Y, Raz A, Nagase H: Autocrine motility factor signaling induces tumor apoptotic resistance by regulations Apaf-1 and Caspase-9 apoptosome expression. Int J Cancer 107: 707–714, 2003CrossRefPubMedGoogle Scholar
  102. 102.
    Silletti S, Raz A: Autocrine motility factor is a growth factor. Biochem Biophys Res Commun 194: 446–457, 1993CrossRefPubMedGoogle Scholar
  103. 103.
    Tsutsumi S, Yanagawa T, Shimura T, Fukumori T, Hogan V, Kuwano H, Raz A: Regulation of cell proliferation by autocrine motility factor/phosphoglucose isomerase signaling. J Biol Chem 278: 32165–32172, 2003CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Tatsuyoshi Funasaka
  • Avraham Raz
    • 1
  1. 1.Tumor Progression and Metastasis Program, Barbara Ann Karmanos Cancer Institute Wayne State University School of MedicineDetroitUSA

Personalised recommendations