Drosophila: A Model for Studying Prostaglandin Signaling



Prostaglandin (PG) synthesis and signaling are conserved in Drosophila melanogaster. PGs are produced downstream of cyclooxygenase or COX enzymes, the targets of nonsteroidal anti-inflammatory drugs. Almost 20 years ago, biochemical studies suggested that Drosophila possess COX activity. Recent efforts utilizing a combination of pharmacological and genetic approaches revealed that PGs have critical functions in Drosophila oogenesis or follicle development. Pxt was identified as the COX-like enzyme and is required for multiple aspects of female fertility, including temporal regulation of both gene expression and actin cytoskeletal remodeling. Here we review the PG synthesis and signaling machinery, the evidence for PG activity in Drosophila, the roles of PGs in flies, primarily focused on oogenic activities, and the conservation of PG function in higher animals. We also point out how studies on PGs in a genetic model system, such as flies, can significantly advance our understanding of the molecular actions of PGs.


Prostaglandins Drosophila Oogenesis Reproduction Actin cytoskeleton Fascin Enabled Cancer Gene amplification 


  1. 1.
    Funk CD (2001) Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294(5548):1871–1875PubMedCrossRefGoogle Scholar
  2. 2.
    Tootle TL (2013) Genetic insights into the in vivo functions of prostaglandin signaling. Int J Biochem Cell Biol 45(8):1629–1632PubMedCrossRefGoogle Scholar
  3. 3.
    Garavito RM, DeWitt DL (1999) The cyclooxygenase isoforms: structural insights into the conversion of arachidonic acid to prostaglandins. Biochim Biophys Acta 1441(2-3):278–287PubMedCrossRefGoogle Scholar
  4. 4.
    Smith WL, DeWitt DL, Garavito RM (2000) Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 69:145–182PubMedCrossRefGoogle Scholar
  5. 5.
    Garavito RM, Mulichak AM (2003) The structure of mammalian cyclooxygenases. Annu Rev Biophys Biomol Struct 32:183–206PubMedCrossRefGoogle Scholar
  6. 6.
    Simmons DL, Botting RM, Hla T (2004) Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev 56(3):387–437PubMedCrossRefGoogle Scholar
  7. 7.
    Smith WL, Urade Y, Jakobsson PJ (2011) Enzymes of the cyclooxygenase pathways of prostanoid biosynthesis. Chem Rev 111(10):5821–5865PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Buchanan FG et al (2003) Prostaglandin E2 regulates cell migration via the intracellular activation of the epidermal growth factor receptor. J Biol Chem 278(37):35451–35457PubMedCrossRefGoogle Scholar
  9. 9.
    Han C, Michalopoulos GK, Wu T (2006) Prostaglandin E2 receptor EP1 transactivates EGFR/MET receptor tyrosine kinases and enhances invasiveness in human hepatocellular carcinoma cells. J Cell Physiol 207(1):261–270PubMedCrossRefGoogle Scholar
  10. 10.
    Pai R et al (2002) Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy. Nat Med 8(3):289–293PubMedCrossRefGoogle Scholar
  11. 11.
    Sales KJ, Maudsley S, Jabbour HN (2004) Elevated prostaglandin EP2 receptor in endometrial adenocarcinoma cells promotes vascular endothelial growth factor expression via cyclic 3′,5′-adenosine monophosphate-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase 1/2 signaling pathways. Mol Endocrinol 18(6):1533–1545PubMedCrossRefGoogle Scholar
  12. 12.
    Sales KJ et al (2004) Expression, localization, and signaling of prostaglandin F receptor in human endometrial adenocarcinoma: regulation of proliferation by activation of the epidermal growth factor receptor and mitogen-activated protein kinase signaling pathways. J Clin Endocrinol Metab 89(2):986–993Google Scholar
  13. 13.
    Ali FY et al (2006) Role of prostacyclin versus peroxisome proliferator-activated receptor beta receptors in prostacyclin sensing by lung fibroblasts. Am J Respir Cell Mol Biol 34(2):242–246PubMedCrossRefGoogle Scholar
  14. 14.
    Forman BM et al (1995) 15-Deoxy-delta 12,14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell 83(5):803–812PubMedCrossRefGoogle Scholar
  15. 15.
    Kliewer SA et al (1995) A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell 83(5):813–819PubMedCrossRefGoogle Scholar
  16. 16.
    Lim H et al (1999) Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPARdelta. Genes Dev 13(12):1561–1574PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Bos CL et al (2004) Prostanoids and prostanoid receptors in signal transduction. Int J Biochem Cell Biol 36(7):1187–1205PubMedCrossRefGoogle Scholar
  18. 18.
    Hirata M et al (1991) Cloning and expression of cDNA for a human thromboxane A2 receptor. Nature 349(6310):617–620PubMedCrossRefGoogle Scholar
  19. 19.
    Hirata T, Narumiya S (2011) Prostanoid receptors. Chem Rev 111(10):6209–6230PubMedCrossRefGoogle Scholar
  20. 20.
    Speirs CK et al (2010) Prostaglandin Gbetagamma signaling stimulates gastrulation movements by limiting cell adhesion through Snai1a stabilization. Development 137(8):1327–1337PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Blomquist GJ et al (1982) Biosynthesis of linoleic acid in a termite, cockroach and cricket. Insect Biochem 12(3):349–353CrossRefGoogle Scholar
  22. 22.
    Keith AD (1967) Fatty acid metabolism in Drosophila melanogaster: interaction between dietary fatty acids and de novo synthesis. Comp Biochem Physiol 21(3):587–600PubMedCrossRefGoogle Scholar
  23. 23.
    Rapport EW, Stanley-Samuelson D, Dadd RH (1983) Ten generations of Drosophila melanogaster reared axenically on a fatty acid-free holidic diet. Arch Insect Biochem Physiol 1(3):243–250CrossRefGoogle Scholar
  24. 24.
    Pages M et al (1986) Cyclooxygenase and lipoxygenase-like activity in Drosophila melanogaster. Prostaglandins 32(5):729–740PubMedCrossRefGoogle Scholar
  25. 25.
    Shen LR et al (2010) Drosophila lacks C20 and C22 PUFAs. J Lipid Res 51(10):2985–2992PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Steinhauer J et al (2009) Drosophila lysophospholipid acyltransferases are specifically required for germ cell development. Mol Biol Cell 20(24):5224–5235PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Carvalho M et al (2012) Effects of diet and development on the Drosophila lipidome. Mol Syst Biol 8:600PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Parisi M, Li R, Oliver B (2011) Lipid profiles of female and male Drosophila. BMC Res Notes 4:198PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Scheitz CJ et al (2013) Heritability and inter-population differences in lipid profiles of Drosophila melanogaster. PLoS One 8(8):e72726PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Kobayashi T, Narumiya S (2002) Function of prostanoid receptors: studies on knockout mice. Prostaglandins Other Lipid Mediat 68-69:557–573PubMedCrossRefGoogle Scholar
  31. 31.
    Stanley D, Kim Y (2011) Prostaglandins and their receptors in insect biology. Front Endocrinol (Lausanne) 2:105Google Scholar
  32. 32.
    Tootle TL, Spradling AC (2008) Drosophila Pxt: a cyclooxygenase-like facilitator of follicle maturation. Development 135(5):839–847PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Subbaramaiah K et al (2002) Cyclooxygenase-2 is overexpressed in HER-2/neu-positive breast cancer: evidence for involvement of AP-1 and PEA3. J Biol Chem 277(21):18649–18657PubMedCrossRefGoogle Scholar
  34. 34.
    Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32(5):1792–1797PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Edgar RC (2004) MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 5:113PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Garavito RM, Malkowski MG, DeWitt DL (2002) The structures of prostaglandin endoperoxide H synthases-1 and -2. Prostaglandins Other Lipid Mediat 68-69:129–152PubMedCrossRefGoogle Scholar
  37. 37.
    Tootle TL et al (2011) Drosophila eggshell production: identification of new genes and coordination by Pxt. PLoS One 6(5):e19943PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Spradling AC (1993) Developmental genetics of oogenesis. In: Martinez-Arias B (ed) The development of Drosophila melanogaster. Cold Spring Harbor Laboratory Press, Plainview, pp 1–70Google Scholar
  39. 39.
    Groen CM et al (2012) Drosophila Fascin is a novel downstream target of prostaglandin signaling during actin remodeling. Mol Biol Cell 23(23):4567–4578PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Spracklen AJ et al (2014) Prostaglandins temporally regulate cytoplasmic actin bundle formation during Drosophila oogenesis. Mol Biol Cell 25(3):397–411PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Cavaliere V et al (2008) Building up the Drosophila eggshell: first of all the eggshell genes must be transcribed. Dev Dyn 237(8):2061–2072PubMedCrossRefGoogle Scholar
  42. 42.
    Claycomb JM, Orr-Weaver TL (2005) Developmental gene amplification: insights into DNA replication and gene expression. Trends Genet 21(3):149–162PubMedCrossRefGoogle Scholar
  43. 43.
    Kim JC et al (2011) Integrative analysis of gene amplification in Drosophila follicle cells: parameters of origin activation and repression. Genes Dev 25(13):1384–1398PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Claycomb JM et al (2004) Gene amplification as a developmental strategy: isolation of two developmental amplicons in Drosophila. Dev Cell 6(1):145–155PubMedCrossRefGoogle Scholar
  45. 45.
    Hudson AM, Cooley L (2002) Understanding the function of actin-binding proteins through genetic analysis of Drosophila oogenesis. Annu Rev Genet 36:455–488PubMedCrossRefGoogle Scholar
  46. 46.
    Bownes M, Hames BD (1978) Genetic analysis of vitellogenesis in Drosophila melanogaster: the identification of a temperature-sensitive mutation affecting one of the yolk proteins. J Embryol Exp Morphol 47:111–120PubMedGoogle Scholar
  47. 47.
    Bownes M, Hodson BA (1980) Mutant Fs(1) 1163 of Drosophila melanogaster alters yolk protein secretion from the fat-body. Mol Gen Genet 180(2):411–418CrossRefGoogle Scholar
  48. 48.
    Gutzeit HO (1986) The role of microfilaments in cytoplasmic streaming in Drosophila follicles. J Cell Sci 80:159–169PubMedGoogle Scholar
  49. 49.
    Theurkauf WE et al (1992) Reorganization of the cytoskeleton during Drosophila oogenesis: implications for axis specification and intercellular transport. Development 115(4):923–936PubMedGoogle Scholar
  50. 50.
    Montell DJ, Yoon WH, Starz-Gaiano M (2012) Group choreography: mechanisms orchestrating the collective movement of border cells. Nat Rev Mol Cell Biol 13(10):631–645PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Guild GM et al (1997) Actin filament cables in Drosophila nurse cells are composed of modules that slide passively past one another during dumping. J Cell Biol 138(4):783–797PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Huelsmann S, Ylanne J, Brown NH (2013) Filopodia-like actin cables position nuclei in association with perinuclear actin in Drosophila nurse cells. Dev Cell 26(6):604–615PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Wheatley S, Kulkarni S, Karess R (1995) Drosophila nonmuscle myosin II is required for rapid cytoplasmic transport during oogenesis and for axial nuclear migration in early embryos. Development 121(6):1937–1946PubMedGoogle Scholar
  54. 54.
    Mahajan-Miklos S, Cooley L (1994) Intercellular cytoplasm transport during Drosophila oogenesis. Dev Biol 165(2):336–351PubMedCrossRefGoogle Scholar
  55. 55.
    Cooley L, Verheyen E, Ayers K (1992) chickadee encodes a profilin required for intercellular cytoplasm transport during Drosophila oogenesis. Cell 69(1):173–184PubMedCrossRefGoogle Scholar
  56. 56.
    Banan A et al (2000) Role of actin cytoskeleton in prostaglandin-induced protection against ethanol in an intestinal epithelial cell line. J Surg Res 88(2):104–113PubMedCrossRefGoogle Scholar
  57. 57.
    Birukova AA et al (2007) Prostaglandins PGE2 and PGI2 promote endothelial barrier enhancement via PKA- and Epac1/Rap1-dependent Rac activation. Exp Cell Res 313(11):2504–2520PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Bulin C et al (2005) Differential effects of vasodilatory prostaglandins on focal adhesions, cytoskeletal architecture, and migration in human aortic smooth muscle cells. Arterioscler Thromb Vasc Biol 25(1):84–89PubMedGoogle Scholar
  59. 59.
    Dormond O et al (2002) Prostaglandin E2 promotes integrin alpha Vbeta 3-dependent endothelial cell adhesion, rac-activation, and spreading through cAMP/PKA-dependent signaling. J Biol Chem 277(48):45838–45846PubMedCrossRefGoogle Scholar
  60. 60.
    Kawada N, Klein H, Decker K (1992) Eicosanoid-mediated contractility of hepatic stellate cells. Biochem J 285(pt 2):367–371PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    Peppelenbosch MP et al (1993) Epidermal growth factor-induced actin remodeling is regulated by 5-lipoxygenase and cyclooxygenase products. Cell 74(3):565–575PubMedCrossRefGoogle Scholar
  62. 62.
    Martineau LC et al (2004) p38 MAP kinase mediates mechanically induced COX-2 and PG EP4 receptor expression in podocytes: implications for the actin cytoskeleton. Am J Physiol Renal Physiol 286(4):F693–F701PubMedCrossRefGoogle Scholar
  63. 63.
    Spracklen AJ, Tootle TL (2013) The utility of stage-specific mid-to-late Drosophila follicle isolation. J Vis Exp 82:50493PubMedGoogle Scholar
  64. 64.
    Kraft R et al (2013) A cell-based fascin bioassay identifies compounds with potential anti-metastasis or cognition-enhancing functions. Dis Model Mech 6(1):217–235PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    Fabian L, Brill JA (2012) Drosophila spermiogenesis: big things come from little packages. Spermatogenesis 2(3):197–212PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Akil M, Amos RS, Stewart P (1996) Infertility may sometimes be associated with NSAID consumption. Br J Rheumatol 35(1):76–78PubMedCrossRefGoogle Scholar
  67. 67.
    Pall M, Friden BE, Brannstrom M (2001) Induction of delayed follicular rupture in the human by the selective COX-2 inhibitor rofecoxib: a randomized double-blind study. Hum Reprod 16(7):1323–1328PubMedCrossRefGoogle Scholar
  68. 68.
    Smith G et al (1996) Reversible ovulatory failure associated with the development of luteinized unruptured follicles in women with inflammatory arthritis taking non-steroidal anti-inflammatory drugs. Br J Rheumatol 35(5):458–462PubMedCrossRefGoogle Scholar
  69. 69.
    Lim H et al (1997) Multiple female reproductive failures in cyclooxygenase 2-deficient mice. Cell 91(2):197–208PubMedCrossRefGoogle Scholar
  70. 70.
    Takahashi T et al (2006) Cyclooxygenase-2-derived prostaglandin E2 directs oocyte maturation by differentially influencing multiple signaling pathways. J Biol Chem 281(48):37117–37129PubMedCrossRefGoogle Scholar
  71. 71.
    Downs SM, Longo FJ (1983) Prostaglandins and preovulatory follicular maturation in mice. J Exp Zool 228(1):99–108PubMedCrossRefGoogle Scholar
  72. 72.
    Lister AL, Van Der Kraak G (2008) An investigation into the role of prostaglandins in zebrafish oocyte maturation and ovulation. Gen Comp Endocrinol 159(1):46–57PubMedCrossRefGoogle Scholar
  73. 73.
    Machado E et al (2007) Prostaglandin signaling and ovarian follicle development in the silkmoth, Bombyx mori. Insect Biochem Mol Biol 37(8):876–885PubMedCrossRefGoogle Scholar
  74. 74.
    Chen WS et al (2001) Tumor invasiveness and liver metastasis of colon cancer cells correlated with cyclooxygenase-2 (COX-2) expression and inhibited by a COX-2-selective inhibitor, etodolac. Int J Cancer 91(6):894–899PubMedCrossRefGoogle Scholar
  75. 75.
    Denkert C et al (2003) Elevated expression of cyclooxygenase-2 is a negative prognostic factor for disease free survival and overall survival in patients with breast carcinoma. Cancer 97(12):2978–2987PubMedCrossRefGoogle Scholar
  76. 76.
    Gallo O et al (2002) Prognostic significance of cyclooxygenase-2 pathway and angiogenesis in head and neck squamous cell carcinoma. Hum Pathol 33(7):708–714PubMedCrossRefGoogle Scholar
  77. 77.
    Khuri FR et al (2001) Cyclooxygenase-2 overexpression is a marker of poor prognosis in stage I non-small cell lung cancer. Clin Cancer Res 7(4):861–867PubMedGoogle Scholar
  78. 78.
    Lyons TR et al (2011) Postpartum mammary gland involution drives progression of ductal carcinoma in situ through collagen and COX-2. Nat Med 17(9):1109–1115PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Rolland PH et al (1980) Prostaglandin in human breast cancer: evidence suggesting that an elevated prostaglandin production is a marker of high metastatic potential for neoplastic cells. J Natl Cancer Inst 64(5):1061–1070PubMedGoogle Scholar
  80. 80.
    Tsujii M, Kawano S, DuBois RN (1997) Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci U S A 94(7):3336–3340PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Yamakita Y, Matsumura F, Yamashiro S (2009) Fascin1 is dispensable for mouse development but is favorable for neonatal survival. Cell Motil Cytoskeleton 66(8):524–534PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Albertson DG (2006) Gene amplification in cancer. Trends Genet 22(8):447–455PubMedCrossRefGoogle Scholar
  83. 83.
    Santarius T et al (2010) A census of amplified and overexpressed human cancer genes. Nat Rev Cancer 10(1):59–64PubMedCrossRefGoogle Scholar
  84. 84.
    Slamon DJ et al (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785):177–182PubMedCrossRefGoogle Scholar
  85. 85.
    Tamma G et al (2003) The prostaglandin E2 analogue sulprostone antagonizes vasopressin-induced antidiuresis through activation of Rho. J Cell Sci 116(pt 16):3285–3294PubMedCrossRefGoogle Scholar
  86. 86.
    Pierce KL et al (1999) Activation of FP prostanoid receptor isoforms leads to Rho-mediated changes in cell morphology and in the cell cytoskeleton. J Biol Chem 274(50):35944–35949PubMedCrossRefGoogle Scholar
  87. 87.
    Bearer EL, Prakash JM, Li Z (2002) Actin dynamics in platelets. Int Rev Cytol 217:137–182PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    Hamberg M, Svensson J, Samuelsson B (1975) Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci U S A 72(8):2994–2998PubMedCentralPubMedCrossRefGoogle Scholar
  89. 89.
    Moncada S, Higgs EA, Vane JR (1977) Human arterial and venous tissues generate prostacyclin (prostaglandin x), a potent inhibitor of platelet aggregation. Lancet 1(8001):18–20PubMedCrossRefGoogle Scholar
  90. 90.
    Kloeze J (1966) Influence of prostaglandins on platelet adhesiveness and platelet aggregation. In: Prostaglandins: proceedings of the second nobel symposium. Almqvist & Wiksell/Interscience, Stockholm/New York/London [etc.]Google Scholar
  91. 91.
    Smith JB et al (1974) Prostaglandin D2 inhibits the aggregation of human platelets. Thromb Res 5(3):291–299PubMedCrossRefGoogle Scholar
  92. 92.
    Willis AL (1974) An enzymatic mechanism for the antithrombotic and antihemostatic actions of aspirin. Science 183(4122):325–327PubMedCrossRefGoogle Scholar
  93. 93.
    Petrucci G et al (2011) Prostaglandin E2 differentially modulates human platelet function through the prostanoid EP2 and EP3 receptors. J Pharmacol Exp Ther 336(2):391–402PubMedCrossRefGoogle Scholar
  94. 94.
    Smith JP et al (2010) PGE2 decreases reactivity of human platelets by activating EP2 and EP4. Thromb Res 126(1):e23–e29PubMedCentralPubMedCrossRefGoogle Scholar
  95. 95.
    Aszodi A et al (1999) The vasodilator-stimulated phosphoprotein (VASP) is involved in cGMP- and cAMP-mediated inhibition of agonist-induced platelet aggregation, but is dispensable for smooth muscle function. EMBO J 18(1):37–48PubMedCentralPubMedCrossRefGoogle Scholar
  96. 96.
    Bearer EL et al (2000) VASP protects actin filaments from gelsolin: an in vitro study with implications for platelet actin reorganizations. Cell Motil Cytoskeleton 47(4):351–364PubMedCentralPubMedCrossRefGoogle Scholar
  97. 97.
    Troys M, Vandekerckhove J, Ampe C (2008) Actin and actin-binding proteins in cancer progression and metastasis. In: Remedios C, Chhabra D (eds) Actin-binding proteins and disease. Springer, New York, pp 229–277CrossRefGoogle Scholar
  98. 98.
    Li A et al (2010) The actin-bundling protein fascin stabilizes actin in invadopodia and potentiates protrusive invasion. Curr Biol 20(4):339–345PubMedCentralPubMedCrossRefGoogle Scholar
  99. 99.
    Qualtrough D et al (2009) The actin-bundling protein fascin is overexpressed in colorectal adenomas and promotes motility in adenoma cells in vitro. Br J Cancer 101(7):1124–1129PubMedCentralPubMedCrossRefGoogle Scholar
  100. 100.
    Chen L et al (2010) Migrastatin analogues target fascin to block tumour metastasis. Nature 464(7291):1062–1066PubMedCentralPubMedCrossRefGoogle Scholar
  101. 101.
    Hall A (2009) The cytoskeleton and cancer. Cancer Metastasis Rev 28(1-2):5–14PubMedCrossRefGoogle Scholar
  102. 102.
    Bae YH et al (2009) Loss of profilin-1 expression enhances breast cancer cell motility by Ena/VASP proteins. J Cell Physiol 219(2):354–364PubMedCentralPubMedCrossRefGoogle Scholar
  103. 103.
    Hu LD et al (2008) EVL (Ena/VASP-like) expression is up-regulated in human breast cancer and its relative expression level is correlated with clinical stages. Oncol Rep 19(4):1015–1020PubMedGoogle Scholar
  104. 104.
    Bear JE, Gertler FB (2009) Ena/VASP: towards resolving a pointed controversy at the barbed end. J Cell Sci 122(pt 12):1947–1953PubMedCentralPubMedCrossRefGoogle Scholar
  105. 105.
    Hashimoto Y, Parsons M, Adams JC (2007) Dual actin-bundling and protein kinase C-binding activities of fascin regulate carcinoma cell migration downstream of Rac and contribute to metastasis. Mol Biol Cell 18(11):4591–4602PubMedCentralPubMedCrossRefGoogle Scholar
  106. 106.
    Vignjevic D et al (2006) Role of fascin in filopodial protrusion. J Cell Biol 174(6):863–875PubMedCentralPubMedCrossRefGoogle Scholar
  107. 107.
    Schoumacher M et al (2010) Actin, microtubules, and vimentin intermediate filaments cooperate for elongation of invadopodia. J Cell Biol 189(3):541–556PubMedCentralPubMedCrossRefGoogle Scholar
  108. 108.
    Yoder BJ et al (2005) The expression of fascin, an actin-bundling motility protein, correlates with hormone receptor-negative breast cancer and a more aggressive clinical course. Clin Cancer Res 11(1):186–192PubMedGoogle Scholar
  109. 109.
    Hashimoto Y, Skacel M, Adams JC (2005) Roles of fascin in human carcinoma motility and signaling: prospects for a novel biomarker? Int J Biochem Cell Biol 37(9):1787–1804PubMedCrossRefGoogle Scholar
  110. 110.
    Chan C et al (2010) Fascin expression predicts survival after potentially curative resection of node-positive colon cancer. Am J Surg Pathol 34(5):656–666PubMedGoogle Scholar
  111. 111.
    Hashimoto Y et al (2004) The prognostic relevance of fascin expression in human gastric carcinoma. Oncology 67(3-4):262–270PubMedCrossRefGoogle Scholar
  112. 112.
    Lee TK et al (2007) Fascin over-expression is associated with aggressiveness of oral squamous cell carcinoma. Cancer Lett 254(2):308–315PubMedCrossRefGoogle Scholar
  113. 113.
    Li X et al (2008) Aberrant expression of cortactin and fascin are effective markers for pathogenesis, invasion, metastasis and prognosis of gastric carcinomas. Int J Oncol 33(1):69–79PubMedGoogle Scholar
  114. 114.
    Okada K et al (2007) Fascin expression is correlated with tumor progression of extrahepatic bile duct cancer. Hepatogastroenterology 54(73):17–21PubMedGoogle Scholar
  115. 115.
    Gertler FB et al (1996) Mena, a relative of VASP and Drosophila enabled, is implicated in the control of microfilament dynamics. Cell 87(2):227–239PubMedCrossRefGoogle Scholar
  116. 116.
    Gertler F, Condeelis J (2011) Metastasis: tumor cells becoming MENAcing. Trends Cell Biol 21(2):81–90PubMedCentralPubMedCrossRefGoogle Scholar
  117. 117.
    Gurzu S et al (2013) The possible role of Mena protein and its splicing-derived variants in embryogenesis, carcinogenesis, and tumor invasion: a systematic review of the literature. Biomed Res Int 2013:365192PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2015

Authors and Affiliations

  1. 1.Anatomy and Cell Biology DepartmentUniversity of Iowa Carver College of MedicineIowa CityUSA

Personalised recommendations