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Role of the EGF-CFC Family in Mammary Gland Development and Neoplasia

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Breast Cancer in the Post-Genomic Era

Part of the book series: Current Clinical Oncology ((CCO))

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Summary

Members of the Epidermal Growth Factor-Cripto-1/FRL-1/Cryptic (EGF-CFC) family, such as human Cripto-1, are important mediators of crucial events that take place during embryonic pattern formation. New evidences from gene expression and transgenic mouse studies have also shown that perturbation of Cripto-1 signaling may lead to cell transformation and tumor formation in vivo. In addition, Cripto-1 is expressed at high levels in a wide variety of human carcinomas including early and late breast cancers. Despite the clear correlation between Cripto-1 overexpression and human and mouse tumors, the exact molecular mechanism of Cripto-1 contribution to the cell transformation process is not clear. Cripto-1 has been shown to activate multiple signaling pathways to promote either differentiation during embryogenesis or cancer growth. In this review we will discuss the multifunction properties of the EGF-CFC family of proteins and the complex network of signaling molecules activated by Cripto-1 focusing in particular on the mammary gland. A better understanding of the intracellular signaling pathways that mediate Cripto-1 activity in human tumors might identify novel points of intervention to target Cripto-1 in human malignancies.

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References

  1. Salomon DS, Bianco C, Ebert AD, et alet al. The EGF-CFC family: novel epidermal growth factor-related proteins in development and cancer. Endocr Relat Cancer 2000;7(4):199–226.

    Article  CAS  Google Scholar 

  2. Bianco C, Strizzi L, Normanno N, Khan N, Salomon DS. Cripto-1: an oncofetal gene with many faces. Curr Top Dev Biol 2005;67:85–133.

    Article  CAS  PubMed  Google Scholar 

  3. Dorey K, Hill CS. A novel Cripto-related protein reveals an essential role for EGF-CFCs in Nodal signalling in Xenopus embryos. Dev Biol 2006;292(2):303–16.

    Article  CAS  PubMed  Google Scholar 

  4. Zhang J, Talbot WS, Schier AF. Positional cloning identifies zebrafish one-eyed pinhead as a permissive EGF-related ligand required during gastrulation. Cell 1998;92(2):241–51.

    Article  CAS  PubMed  Google Scholar 

  5. Colas JF, Schoenwolf GC. Subtractive hybridization identifies chick-cripto, a novel EGF-CFC ortholog expressed during gastrulation, neurulation and early cardiogenesis. Gene 2000;255(2):205–17.

    Article  CAS  PubMed  Google Scholar 

  6. Schlange T, Schnipkoweit I, Andree B, et al. Chick CFC controls Lefty1 expression in the embryonic midline and nodal expression in the lateral plate. Dev Biol 2001;234(2):376–89.

    Article  CAS  PubMed  Google Scholar 

  7. Ding J, Yang L, Yan YT, et alet al. Cripto is required for correct orientation of the anterior-posterior axis in the mouse embryo. Nature 1998;395(6703):702–7.

    Article  CAS  PubMed  Google Scholar 

  8. Shen MM, Wang H, Leder P. A differential display strategy identifies Cryptic, a novel EGF-related gene expressed in the axial and lateral mesoderm during mouse gastrulation. Development 1997;124(2):429–42.

    CAS  PubMed  Google Scholar 

  9. Ciccodicola A, Dono R, Obici S, Simeone A, Zollo M, Persico MG. Molecular characterization of a gene of the ‘EGF family’ expressed in undifferentiated human NTERA2 teratocarcinoma cells. EMBO J 1989;8(7):1987–91.

    CAS  PubMed  Google Scholar 

  10. Bamford RN, Roessler E, Burdine RD, et alet al. Loss-of-function mutations in the EGF-CFC gene CFC1 are associated with human left-right laterality defects. Nat Genet 2000;26(3):365–9.

    Article  CAS  PubMed  Google Scholar 

  11. Shen MM. Nodal signaling: developmental roles and regulation. Development 2007;134(6):1023–34.

    Article  CAS  PubMed  Google Scholar 

  12. Duboc V, Rottinger E, Besnardeau L, Lepage T. Nodal and BMP2/4 signaling organizes the oral-aboral axis of the sea urchin embryo. Dev Cell 2004;6(3):397–410.

    Article  CAS  PubMed  Google Scholar 

  13. Minchiotti G, Manco G, Parisi S, Lago CT, Rosa F, Persico MG. Structure–function analysis of the EGF-CFC family member Cripto identifies residues essential for nodal signalling. Development 2001;128(22):4501–10.

    CAS  PubMed  Google Scholar 

  14. Hentschke M, Kurth I, Borgmeyer U, Hubner CA. Germ cell nuclear factor is a repressor of CRIPTO-1 and CRIPTO-3. J Biol Chem 2006;281(44):33497–504.

    Article  CAS  PubMed  Google Scholar 

  15. Lohmeyer M, Harrison PM, Kannan S, et alet al. Chemical synthesis, structural modeling, and biological activity of the epidermal growth factor-like domain of human cripto. Biochemistry 1997;36(13):3837–45.

    Article  CAS  PubMed  Google Scholar 

  16. Seno M, DeSantis M, Kannan S, et alet al. Purification and characterization of a recombinant human cripto-1 protein. Growth Factors 1998;15(3):215–29.

    Article  CAS  PubMed  Google Scholar 

  17. Marasco D, Saporito A, Ponticelli S, et alet al. Chemical synthesis of mouse cripto CFC variants. Proteins 2006;64(3):779–88.

    Article  CAS  PubMed  Google Scholar 

  18. Foley SF, van Vlijmen HW, Boynton RE, et alet al. The CRIPTO/FRL-1/CRYPTIC (CFC) domain of human Cripto Functional and structural insights through disulfide structure analysis. Eur J Biochem 2003;270(17):3610–18.

    Article  CAS  PubMed  Google Scholar 

  19. Calvanese L, Saporito A, Marasco D, et alet al. Solution structure of mouse Cripto CFC domain and its inactive variant Trp107Ala. J Med Chem 2006;49(24):7054–62.

    Article  CAS  PubMed  Google Scholar 

  20. Schiffer SG, Foley S, Kaffashan A, et alet al. Fucosylation of Cripto is required for its ability to facilitate nodal signaling. J Biol Chem 2001;276(41):37769–78.

    CAS  PubMed  Google Scholar 

  21. Shi S, Ge C, Luo Y, Hou X, Haltiwanger RS, Stanley P. The threonine that carries fucose, but not fucose, is required for Cripto to facilitate Nodal signaling. J Biol Chem 2007;282(28):20133–41.

    Article  CAS  PubMed  Google Scholar 

  22. Yan YT, Liu JJ, Luo Y, et alet al. Dual roles of Cripto as a ligand and coreceptor in the nodal signaling pathway. Mol Cell Biol 2002;22(13):4439–49.

    Article  CAS  PubMed  Google Scholar 

  23. Minchiotti G, Parisi S, Liguori G, et alet al. Membrane-anchorage of Cripto protein by glycosylphosphatidylinositol and its distribution during early mouse development. Mech Dev 2000;90(2):133–42.

    Article  CAS  PubMed  Google Scholar 

  24. Watanabe K, Bianco C, Strizzi L, et alet al. Growth factor induction of cripto-1 shedding by GPI-phospholipase D and enhancement of endothelial cell migration. J Biol Chem 2007;282(43):31643–55.

    Article  CAS  PubMed  Google Scholar 

  25. Watanabe K, Hamada S, Bianco C, et alet al. Requirement of glycosylphosphatidylinositol anchor of cripto-1 for ‘trans’ activity as a nodal co-receptor. J Biol Chem 2007;282(49):35772–86.

    Article  CAS  PubMed  Google Scholar 

  26. Rampal R, Luther KB, Haltiwanger RS. Notch signaling in normal and disease States: possible therapies related to glycosylation. Curr Mol Med 2007;7(4):427–45.

    Article  CAS  PubMed  Google Scholar 

  27. Rabbani SA, Mazar AP, Bernier SM, et alet al. Structural requirements for the growth factor activity of the amino-terminal domain of urokinase. J Biol Chem 1992;267(20):14151–6.

    CAS  PubMed  Google Scholar 

  28. Joutel A, Corpechot C, Ducros A, et alet al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 1996;383(6602):707–10.

    Article  CAS  PubMed  Google Scholar 

  29. Bianco C, Strizzi L, Mancino M, et alet al. Regulation of Cripto-1 signaling and biological activity by Caveolin-1 in mammary epithelial cells. Am J Pathol 2008;172:345–357.

    Article  CAS  PubMed  Google Scholar 

  30. Parisi S, D’Andrea D, Lago CT, Adamson ED, Persico MG, Minchiotti G. Nodal-dependent Cripto signaling promotes cardiomyogenesis and redirects the neural fate of embryonic stem cells. J Cell Biol 2003;163(2):303–14.

    Article  CAS  PubMed  Google Scholar 

  31. Bianco C, Strizzi L, Rehman A, et al. A Nodal- and ALK4-independent signaling pathway activated by Cripto-1 through Glypican-1 and c-Src. Cancer Res 2003;63(6):1192–7.

    CAS  PubMed  Google Scholar 

  32. Bianco C, Kannan S, De Santis M, et al. Cripto-1 indirectly stimulates the tyrosine phosphorylation of erb B-4 through a novel receptor. J Biol Chem 1999;274(13):8624–9.

    Article  CAS  PubMed  Google Scholar 

  33. Schier AF. Nodal signaling in vertebrate development. Annu Rev Cell Dev Biol 2003;19:589–621.

    Article  CAS  PubMed  Google Scholar 

  34. Cheng SK, Olale F, Bennett JT, Brivanlou AH, Schier AF. EGF-CFC proteins are essential coreceptors for the TGF-beta signals Vg1 and GDF1. Genes Dev 2003;17(1):31–6.

    Article  CAS  PubMed  Google Scholar 

  35. Chen C, Ware SM, Sato A, et alet al. The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo. Development 2006;133(2):319–29.

    Article  CAS  PubMed  Google Scholar 

  36. Andersson O, Bertolino P, Ibanez CF. Distinct and cooperative roles of mammalian Vg1 homologs GDF1 and GDF3 during early embryonic development. Dev Biol 2007;311(2):500–11.

    Article  CAS  PubMed  Google Scholar 

  37. Yeo C, Whitman M. Nodal signals to Smads through Cripto-dependent and Cripto-independent mechanisms. Mol Cell 2001;7(5):949–57.

    Article  CAS  PubMed  Google Scholar 

  38. Attisano L, Silvestri C, Izzi L, Labbe E. The transcriptional role of Smads and FAST (FoxH1) in TGFbeta and activin signalling. Mol Cell Endocrinol 2001;180(1–2):3–11.

    Article  CAS  PubMed  Google Scholar 

  39. Yamamoto M, Mine N, Mochida K, et alet al. Nodal signaling induces the midline barrier by activating Nodal expression in the lateral plate. Development 2003;130(9):1795–804.

    Article  CAS  PubMed  Google Scholar 

  40. Shen MM, Schier AF. The EGF-CFC gene family in vertebrate development. Trends Genet 2000;16(7):303–9.

    Article  CAS  PubMed  Google Scholar 

  41. Reissmann E, Jornvall H, Blokzijl A, et alet al. The orphan receptor ALK7 and the Activin receptor ALK4 mediate signaling by Nodal proteins during vertebrate development. Genes Dev 2001;15(15):2010–22.

    Article  CAS  PubMed  Google Scholar 

  42. Gray PC, Shani G, Aung K, Kelber J, Vale W. Cripto binds transforming growth factor beta (TGF-beta) and inhibits TGF-beta signaling. Mol Cell Biol 2006;26(24):9268–78.

    Article  CAS  PubMed  Google Scholar 

  43. Harms PW, Chang C. Tomoregulin-1 (TMEFF1) inhibits nodal signaling through direct binding to the nodal coreceptor Cripto. Genes Dev 2003;17(21):2624–9.

    Article  CAS  PubMed  Google Scholar 

  44. Tanegashima K, Haramoto Y, Yokota C, Takahashi S, Asashima M. Xantivin suppresses the activity of EGF-CFC genes to regulate nodal signaling. Int J Dev Biol 2004;48(4):275–83.

    Article  CAS  PubMed  Google Scholar 

  45. Uchida T, Wada K, Akamatsu T, et alet al. A novel epidermal growth factor-like molecule containing two follistatin modules stimulates tyrosine phosphorylation of erbB-4 in MKN28 gastric cancer cells. Biochem Biophys Res Commun 1999;266(2):593–602.

    Article  CAS  PubMed  Google Scholar 

  46. Cheng SK, Olale F, Brivanlou AH, Schier AF. Lefty blocks a subset of TGFbeta signals by antagonizing EGF-CFC coreceptors. PLoS Biol 2004;2(2):E30.

    Article  PubMed  CAS  Google Scholar 

  47. Chen C, Shen MM. Two modes by which Lefty proteins inhibit nodal signaling. Curr Biol 2004;14(7):618–24.

    Article  CAS  PubMed  Google Scholar 

  48. Adkins HB, Bianco C, Schiffer SG, et alet al. Antibody blockade of the Cripto CFC domain suppresses tumor cell growth in vivo. J Clin Invest 2003;112(4):575–87.

    CAS  PubMed  Google Scholar 

  49. Gray PC, Harrison CA, Vale W. Cripto forms a complex with activin and type II activin receptors and can block activin signaling. Proc Natl Acad Sci USA 2003;100(9):5193–8.

    Article  CAS  PubMed  Google Scholar 

  50. Mancino M, Strizzi L, Wechselberger C, et alet al. Regulation of human cripto-1 gene expression by TGF-beta1 and BMP-4 in embryonal and colon cancer cells. J Cell Physiol 2008;215:192–203.

    Article  CAS  PubMed  Google Scholar 

  51. Shani G, Fischer WH, Justice NJ, Kelber JA, Vale W, Gray PC. GRP78 and Cripto form a complex at the cell surface and collaborate to inhibit TGF-β signaling and enhance cell growth. Mol Cell Biol 2008;28:666–677.

    Article  CAS  PubMed  Google Scholar 

  52. Li J, Lee AS. Stress induction of GRP78/BiP and its role in cancer. Curr Mol Med 2006;6(1):45–54.

    Article  CAS  PubMed  Google Scholar 

  53. Lee AS. GRP78 induction in cancer: therapeutic and prognostic implications. Cancer Res 2007;67(8):3496–9.

    Article  CAS  PubMed  Google Scholar 

  54. Lee E, Nichols P, Spicer D, Groshen S, Yu MC, Lee AS. GRP78 as a novel predictor of responsiveness to chemotherapy in breast cancer. Cancer Res 2006;66(16):7849–53.

    Article  CAS  PubMed  Google Scholar 

  55. De Santis ML, Kannan S, Smith GH, et alet al. Cripto-1 inhibits beta-casein expression in mammary epithelial cells through a p21ras-and phosphatidylinositol 3′-kinase-dependent pathway. Cell Growth Differ 1997;8(12):1257–66.

    CAS  PubMed  Google Scholar 

  56. Ebert AD, Wechselberger C, Frank S, et al. Cripto-1 induces phosphatidylinositol 3′-kinase-dependent phosphorylation of AKT and glycogen synthase kinase 3beta in human cervical carcinoma cells. Cancer Res 1999;59(18):4502–5.

    CAS  PubMed  Google Scholar 

  57. Bianco C, Normanno N, De Luca A, et al. Detection and localization of Cripto-1 binding in mouse mammary epithelial cells and in the mouse mammary gland using an immunoglobulin-cripto-1 fusion protein. J Cell Physiol 2002;190(1):74–82.

    Article  CAS  PubMed  Google Scholar 

  58. Bianco C, Adkins HB, Wechselberger C, et al. Cripto-1 activates nodal- and ALK4-dependent and -independent signaling pathways in mammary epithelial Cells. Mol Cell Biol 2002;22(8):2586–97.

    Article  CAS  PubMed  Google Scholar 

  59. Morkel M, Huelsken J, Wakamiya M, et al. Beta-catenin regulates Cripto- and Wnt3-dependent gene expression programs in mouse axis and mesoderm formation. Development 2003;130(25):6283–94.

    Article  CAS  PubMed  Google Scholar 

  60. Hamada S, Watanabe K, Hirota M, et al. beta-Catenin/TCF/LEF regulate expression of the short form human Cripto-1. Biochem Biophys Res Commun 2007;355(1):240–4.

    Article  CAS  PubMed  Google Scholar 

  61. Segditsas S, Tomlinson I. Colorectal cancer and genetic alterations in the Wnt pathway. Oncogene 2006;25(57):7531–7.

    Article  CAS  PubMed  Google Scholar 

  62. Tao Q, Yokota C, Puck H, et al. Maternal wnt11 activates the canonical wnt signaling pathway required for axis formation in Xenopus embryos. Cell 2005;120(6):857–71.

    Article  CAS  PubMed  Google Scholar 

  63. Zamparini AL, Watts T, Gardner CE, Tomlinson SR, Johnston GI, Brickman JM. Hex acts with beta-catenin to regulate anteroposterior patterning via a Groucho-related co-repressor and Nodal. Development 2006;133(18):3709–22.

    Article  CAS  PubMed  Google Scholar 

  64. Krebs LT, Iwai N, Nonaka S, et al. Notch signaling regulates left-right asymmetry determination by inducing Nodal expression. Genes Dev 2003;17(10):1207–12.

    Article  CAS  PubMed  Google Scholar 

  65. Dono R, Scalera L, Pacifico F, Acampora D, Persico MG, Simeone A. The murine cripto gene: expression during mesoderm induction and early heart morphogenesis. Development 1993;118(4):1157–68.

    CAS  PubMed  Google Scholar 

  66. Johnson SE, Rothstein JL, Knowles BB. Expression of epidermal growth factor family gene members in early mouse development. Dev Dyn 1994;201(3):216–26.

    CAS  PubMed  Google Scholar 

  67. Xu C, Liguori G, Persico MG, Adamson ED. Abrogation of the Cripto gene in mouse leads to failure of postgastrulation morphogenesis and lack of differentiation of cardiomyocytes. Development 1999;126(3):483–94.

    CAS  PubMed  Google Scholar 

  68. Gritsman K, Zhang J, Cheng S, Heckscher E, Talbot WS, Schier AF. The EGF-CFC protein one-eyed pinhead is essential for nodal signaling. Cell 1999;97(1):121–32.

    Article  CAS  PubMed  Google Scholar 

  69. Schier AF, Shen MM. Nodal signalling in vertebrate development. Nature 2000;403(6768):385–9.

    Article  CAS  PubMed  Google Scholar 

  70. Warga RM, Kane DA. One-eyed pinhead regulates cell motility independent of Squint/Cyclops signaling. Dev Biol 2003;261(2):391–411.

    Article  CAS  PubMed  Google Scholar 

  71. Yan YT, Gritsman K, Ding J, et al. Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation. Genes Dev 1999;13(19):2527–37.

    Article  CAS  PubMed  Google Scholar 

  72. Saijoh Y, Adachi H, Sakuma R, et al. Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes the transcription factor FAST2. Mol Cell 2000;5(1):35–47.

    Article  CAS  PubMed  Google Scholar 

  73. Gaio U, Schweickert A, Fischer A, et al. A role of the cryptic gene in the correct establishment of the left-right axis. Curr Biol 1999;9(22):1339–42.

    Article  CAS  PubMed  Google Scholar 

  74. Schier AF, Talbot WS. Nodal signaling and the zebrafish organizer. Int J Dev Biol 2001;45(1):289–97.

    CAS  PubMed  Google Scholar 

  75. de la Cruz JM, Bamford RN, Burdine RD, et al. A loss-of-function mutation in the CFC domain of TDGF1 is associated with human forebrain defects. Hum Genet 2002;110(5):422–8.

    Article  PubMed  Google Scholar 

  76. Kenney NJ, Huang RP, Johnson GR, et al. Detection and location of amphiregulin and Cripto-1 expression in the developing postnatal mouse mammary gland. Mol Reprod Dev 1995;41(3):277–86.

    Article  CAS  PubMed  Google Scholar 

  77. Kenney NJ, Adkins HB, Sanicola M. Nodal and cripto-1: embryonic pattern formation genes involved in mammary gland development and tumorigenesis. J Mammary Gland Biol Neoplasia 2004;9(2):133–44.

    Article  PubMed  Google Scholar 

  78. Bianco C, Wechselberger C, Ebert A, Khan NI, Sun Y, Salomon DS. Identification of Cripto-1 in human milk. Breast Cancer Res Treat 2001;66(1):1–7.

    Article  CAS  PubMed  Google Scholar 

  79. Brandt R, Normanno N, Gullick WJ, et al. Identification and biological characterization of an epidermal growth factor-related protein: cripto-1. J Biol Chem 1994;269(25):17320–8.

    CAS  PubMed  Google Scholar 

  80. Ciardiello F, Dono R, Kim N, Persico MG, Salomon DS. Expression of cripto, a novel gene of the epidermal growth factor gene family, leads to in vitro transformation of a normal mouse mammary epithelial cell line. Cancer Res 1991;51(3):1051–4.

    CAS  PubMed  Google Scholar 

  81. Kenney N, Smith G, Johnson M, Rosemberg K, Salomon DS, Dickson R. Cripto-1 activity in the intact and ovariectomized virgin mouse mammary gland. Pathogenesis 1997;1:57–71.

    CAS  Google Scholar 

  82. Normanno N, De Luca A, Bianco C, et al. Cripto-1 overexpression leads to enhanced invasiveness and resistance to anoikis in human MCF-7 breast cancer cells. J Cell Physiol 2004;198(1):31–9.

    Article  CAS  PubMed  Google Scholar 

  83. Thiery JP, Chopin D. Epithelial cell plasticity in development and tumor progression. Cancer Metastasis Rev 1999;18(1):31–42.

    Article  CAS  PubMed  Google Scholar 

  84. Wechselberger C, Strizzi L, Kenney N, et al. Human Cripto-1 overexpression in the mouse mammary gland results in the development of hyperplasia and adenocarcinoma. Oncogene 2005;24(25):4094–105.

    CAS  PubMed  Google Scholar 

  85. Strizzi L, Bianco C, Normanno N, et al. Epithelial mesenchymal transition is a characteristic of hyperplasias and tumors in mammary gland from MMTV-Cripto-1 transgenic mice. J Cell Physiol 2004;201(2):266–76.

    Article  CAS  PubMed  Google Scholar 

  86. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2002;2(6):442–54.

    Article  CAS  PubMed  Google Scholar 

  87. Henderson BR, Fagotto F. The ins and outs of APC and beta-catenin nuclear transport. EMBO Rep 2002;3(9):834–9.

    Article  CAS  PubMed  Google Scholar 

  88. Sun Y, Strizzi L, Raafat A, et al. Overexpression of human Cripto-1 in transgenic mice delays mammary gland development and differentiation and induces mammary tumorigenesis. Am J Pathol 2005;167(2):585–97.

    Article  CAS  PubMed  Google Scholar 

  89. Miyoshi K, Rosner A, Nozawa M, et al. Activation of different Wnt/beta-catenin signaling components in mammary epithelium induces transdifferentiation and the formation of pilar tumors. Oncogene 2002;21(36):5548–56.

    Article  CAS  PubMed  Google Scholar 

  90. Miyoshi K, Shillingford JM, Le Provost F, et al. Activation of beta-catenin signaling in differentiated mammary secretory cells induces transdifferentiation into epidermis and squamous metaplasias. Proc Natl Acad Sci USA 2002;99(1):219–24.

    Article  CAS  PubMed  Google Scholar 

  91. Polakis P. Wnt signaling and cancer. Genes Dev 2000;14(15):1837–51.

    CAS  PubMed  Google Scholar 

  92. Normanno N, Kim N, Wen D, et al. Expression of messenger RNA for amphiregulin, heregulin, and cripto-1, three new members of the epidermal growth factor family, in human breast carcinomas. Breast Cancer Res Treat 1995;35(3):293–7.

    Article  CAS  PubMed  Google Scholar 

  93. Dublin EA, Bobrow LG, Barnes DM, Gullick WJ. Amphiregulin and cripto-1 overexpression in breast cancer: relationship with prognosis and clinical and molecular variables. Int J Oncol 1995;7:617–22.

    CAS  Google Scholar 

  94. Panico L, D’Antonio A, Salvatore G, et al. Differential immunohistochemical detection of transforming growth factor alpha, amphiregulin and CRIPTO in human normal and malignant breast tissues. Int J Cancer 1996;65(1):51–6.

    Article  CAS  PubMed  Google Scholar 

  95. Qi CF, Liscia DS, Normanno N, et al. Expression of transforming growth factor alpha, amphiregulin and cripto-1 in human breast carcinomas. Br J Cancer 1994;69(5):903–10.

    Article  CAS  PubMed  Google Scholar 

  96. Gong YP, Yarrow PM, Carmalt HL, et al. Overexpression of Cripto and its prognostic significance in breast cancer: a study with long-term survival. Eur J Surg Oncol 2007;33(4):438–43.

    Article  CAS  PubMed  Google Scholar 

  97. Carmalt HL, Gong YP, Yarrow PM, Lin BP, Xing PX, Gillett DJ. Bs10 the prognostic significance of the overexpression of the growth factor cripto in patients with breast cancer. ANZ J Surg 2007;77 Suppl 1:A3.

    Article  Google Scholar 

  98. Srinivasan R, Gillett CE, Barnes DM, Gullick WJ. Nuclear expression of the c-erbB-4/HER-4 growth factor receptor in invasive breast cancers. Cancer Res 2000;60(6):1483–7.

    CAS  PubMed  Google Scholar 

  99. Bianco C, Strizzi L, Mancino M, et al. Identification of cripto-1 as a novel serologic marker for breast and colon cancer. Clin Cancer Res 2006;12(17):5158–64.

    Article  CAS  PubMed  Google Scholar 

  100. Zeisberg M, Kalluri R. The role of epithelial-to-mesenchymal transition in renal fibrosis. J Mol Med 2004;82(3):175–81.

    Article  PubMed  Google Scholar 

  101. Willis BC, Liebler JM, Luby-Phelps K, et al. Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-beta1: potential role in idiopathic pulmonary fibrosis. Am J Pathol 2005;166(5):1321–32.

    Article  CAS  PubMed  Google Scholar 

  102. Liu Y. Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention. J Am Soc Nephrol 2004;15(1):1–12.

    Article  CAS  PubMed  Google Scholar 

  103. Strizzi L, Bianco C, Raafat A, et al. Netrin-1 regulates invasion and migration of mouse mammary epithelial cells overexpressing Cripto-1 in vitro and in vivo. J Cell Sci 2005;118 (Part 20):4633–43.

    Article  CAS  PubMed  Google Scholar 

  104. Normanno N, Bianco C, Damiano V, et al. Growth inhibition of human colon carcinoma cells by combinations of anti-epidermal growth factor-related growth factor antisense oligonucleotides. Clin Cancer Res 1996;2(3):601–9.

    CAS  PubMed  Google Scholar 

  105. Hu XF, Xing PX. Cripto as a target for cancer immunotherapy. Expert Opin Ther Targets 2005;9(2):383–94.

    Article  CAS  PubMed  Google Scholar 

  106. De Luca A, Casamassimi A, Selvam MP, et al. EGF-related peptides are involved in the proliferation and survival of MDA-MB-468 human breast carcinoma cells. Int J Cancer 1999;80(4):589–94.

    Article  CAS  PubMed  Google Scholar 

  107. Casamassimi A, De Luca A, Agrawal S, Stromberg K, Salomon DS, Normanno N. EGF-related antisense oligonucleotides inhibit the proliferation of human ovarian carcinoma cells. Ann Oncol 2000;11(3):319–25.

    Article  CAS  PubMed  Google Scholar 

  108. De Luca A, Arra C, D’Antonio A, et al. Simultaneous blockage of different EGF-like growth factors results in efficient growth inhibition of human colon carcinoma xenografts. Oncogene 2000;19(51):5863–71.

    Article  CAS  PubMed  Google Scholar 

  109. Normanno N, De Luca A, Maiello MR, Bianco C, Mancino M, Strizzi L, Arra C, Ciardiello F, Agrawal S, Salomon DS. Cripto-1: a novel target for therapeutic intervention in human carcinoma. Int J Oncol 2004;25(4):1013–20.

    CAS  PubMed  Google Scholar 

  110. Bianco C, Strizzi L, Ebert A, Chang C, Rehman A, Normanno N, Guedez L, Salloum R, Ginsburg E, Sun Y, Khan N, Hirota M, Wallace-Jones B, Wechselberger C, Vonderhaar BK, Tosato G, Stetler-Stevenson WG, Sanicola M, Salomon DS. Role of human cripto-1 in tumor angiogenesis. J Natl Cancer Inst 2005;97(2):132–41.

    Article  CAS  PubMed  Google Scholar 

  111. Xing PX, Hu XF, Pietersz GA, Hosick HL, McKenzie IF. Cripto: a novel target for antibody-based cancer immunotherapy. Cancer Res 2004;64(11):4018–23.

    Article  CAS  PubMed  Google Scholar 

  112. Hu XF, Li J, Yang E, Vandervalk S, Xing PX. Anti-Cripto Mab inhibit tumour growth and overcome MDR in a human leukaemia MDR cell line by inhibition of Akt and activation of JNK/SAPK and bad death pathways. Br J Cancer 2007;96(6):918–27.

    Article  CAS  PubMed  Google Scholar 

  113. Topczewska JM, Postovit LM, Margaryan NV, Sam A, Hess AR, Wheaton WW, Nickoloff BJ, Topczewski J, Hendrix MJ. Embryonic and tumorigenic pathways converge via Nodal signaling: role in melanoma aggressiveness. Nat Med 2006;12(8):925–32.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Children’s Memorial Research Center, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 2300 Children’s Plaza, Box 222, Chicago, IL, 60614-3394, USA

    Luigi Strizzi

  2. Mammary Biology and Tumorigenesis Laboratory, NCI/NIH, 37 Convent Drive, Bethesda, MD, 20892, USA

    Kazuhide Watanabe, Mario Mancino, David S. Salomon & Caterina Bianco

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  1. Luigi Strizzi
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  2. Kazuhide Watanabe
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  3. Mario Mancino
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  4. David S. Salomon
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  5. Caterina Bianco
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    © 2009 Humana Press, a part of Springer Science+Business Media, LLC

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    Strizzi, L., Watanabe, K., Mancino, M., Salomon, D.S., Bianco, C. (2009). Role of the EGF-CFC Family in Mammary Gland Development and Neoplasia. In: Giordano, A., Normanno, N. (eds) Breast Cancer in the Post-Genomic Era. Current Clinical Oncology. Humana Press. https://doi.org/10.1007/978-1-60327-945-1_6

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    • DOI: https://doi.org/10.1007/978-1-60327-945-1_6

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