El papel de Notch, Hh y Wnt en el desarrollo del cáncer de pulmón.

The role of Notch, Hh and Wnt in lung cancer development.

Publicado 2012-09-01

Abrir | Descargar
PDF FLIP
Número
Vol. 1 Núm. 3 (2012): Septiembre
Sección
Artículo especial
Cómo citar
El papel de Notch, Hh y Wnt en el desarrollo del cáncer de pulmón.
Rev. colomb. hematol. oncol. [Internet]. 2012 Sep. 1 [cited 2024 Dec. 26];1(3):51-62. Disponible en: https://doi.org/10.51643/22562915.313
DOI

https://doi.org/10.51643/22562915.313
Dimensions
PlumX
Licencia
Creative Commons License

Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial-CompartirIgual 4.0.

Andrés Felipe Cardona
Fundación Santa Fe de Bogotá
    Noemí Reguart
    Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer (FICMAC)
      Mostrar biografía de los autores

      Andrés Felipe Cardona,

      Clinical and Translational Oncology Group, Institute of Oncology, Fundación Santa Fe de Bogotá (Bogotá, Colombia).

      Noemí Reguart,

      Foundation for Clinical and Applied Cancer Research (FICMAC) (Bogotá, Colombia).

      Hedgehog (Hh), Notch and Wingless-Int (Wnt) are signalling pathways highly conserved among species, essential for embryonic development and progenitor cell fates. All three of these pathways participate in lung development as well as airway epithelial repair process. But interestingly aberrant activation of these pathways is observed in a large variety of cancers, suggesting its potential contribution in the evolution and maintenance of a malignant phenotype. New evidence implicates malignant transformation of the neuroendocrine lineage with aberrant Hedgehog pathway activation, whereas Notch and Wnt signalling may be important in other airway cell types. Bearing in mind the importance of the new theory of tumor formation based on stem-cells rather than on the stochastic model of carcinogenesis, it is not surprising that there has been increasing interest in these genes directly implicated in the stem-cell renewal process. Currently drug design strategies are focus on targeting these signalling pathways and may provide therapeutic opportunities in lung cancer. This review focuses on Hh, Notch Wnt signalling pathways and gives more insight about its role in lung tumorigenesis.

      Visitas del artículo 163 | Visitas PDF 197

      1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74-108.
      2. Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, et al. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science, 1997;275(5307):1787-90.
      3. Dahmen RP, Koch A, Denkhaus D, Tonn JC, Sörensen N, Berthold F, et al. Deletions of AXIN1, a component of the WNT/ wingless pathway, in sporadic medulloblastomas. Cancer Res, 2001;61(19):7039-43.
      4. Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, et al. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science. 1997;275(5307):1784-7.
      5. Liu H, Kho AT, Kohane IS, Sun Y. Predicting survival within the lung cancer histopathological hierarchy using a multi-scale genomic model of development. PLoS Med. 2006;3(7):e232.
      6. Kitagawa H, Goto A, Niki T, Hironaka M, Nakajima J, Fukayama M. Lung adenocarcinoma associated with atypical adenomatous hyperplasia. A clinicopathological study with special reference to smoking and cancer multiplicity. Pathol Int. 2003;53(12):823-7.
      7. Licchesi JD, Westra WH, Hooker CM, Machida EO, Baylin SB, Herman JG. Epigenetic alteration of Wnt pathway antagonists in progressive glandular neoplasia of the lung. Carcinogenesis. 2008;29(5):895-904.
      8. Lemjabbar-Alaoui H, Dasari V, Sidhu SS, Mengistab A, Finkbeiner W, Gallup M, et al. Wnt and Hedgehog are critical mediators of cigarette smoke-induced lung cancer. PLoS One. 2006;1:e93.
      9. Taipale J, Beachy PA. The Hedgehog and Wnt signalling pathways in cancer. Nature. 2001;411(6835):349-54.
      10. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105-111.
      11. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3(7):730-7.
      12. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003;100(7):3983-8.
      13. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005;65(23):10946-51.
      14. Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell. 2005;121(6):823-35.
      15. Ling TY, Kuo MD, Li CL, Yu AL, Huang YH, Wu TJ, et al. Identification of pulmonary Oct-4+ stem/progenitor cells and demonstration of their susceptibility to SARS coronavirus (SARS-CoV) infection in vitro. Proc Natl Acad Sci USA. 2006;103(25):9530- 5.
      16. Ventura JJ, Tenbaum S, Perdiguero E, Huth M, Guerra C, Barbacid M, et al. p38alpha MAP kinase is essential in lung stem and progenitor cell proliferation and differentiation. Nat Genet. 2007;39(6):750-8.
      17. Yanagi S, Kishimoto H, Kawahara K, Sasaki T, Sasaki M, Nishio M, et al. Pten controls lung morphogenesis, bronchioalveolar stem cells, and onset of lung adenocarcinomas in mice. J Clin Invest. 2007;117(10):2929-40.
      18. Pepicelli CV, Lewis PM, McMahon AP. Sonic hedgehog regulates branching morphogenesis in the mammalian lung. Curr Biol. 1998;8(19):1083-6.
      19. Moustakas A, Heldin CH. Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci. 2007;98(10):1512-20.
      20. Winn RA, Van Scoyk M, Hammond M, Rodriguez K, Crossno JT Jr, Heasley LE, et al. Antitumorigenic effect of Wnt 7a and Fzd 9 in non-small cell lung cancer cells is mediated through ERK5-dependent activation of peroxisome proliferator-activated receptor gamma. J Biol Chem. 2006;281(37):26943-50.
      21. Kuo CT, Morrisey EE, Anandappa R, Sigrist K, Lu MM, Parmacek MS, et al. GATA4 transcription factor is required for ventral morphogenesis and heart tube formation. Genes Dev. 1997;11(8):1048-60.
      22. Lako M, Strachan T, Bullen P, Wilson DI, Robson SC, Lindsay S. Isolation, characterisation and embryonic expression of WNT11, a gene which maps to 11q13.5 and has possible roles in the development of skeleton, kidney and lung. Gene. 1998;219(1- 2):101-10.
      23. Kimura S, Hara Y, Pineau T, Fernandez-Salguero P, Fox CH, Ward JM, et al. The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. Genes Dev. 1996;10(1):60-9.
      24. Hui CC, Slusarski D, Platt KA, Holmgren R, Joyner AL. Expression of three mouse homologs of the Drosophila segment polarity gene cubitus interruptus, Gli, Gli-2, and Gli-3, in ectodermand mesoderm-derived tissues suggests multiple roles during postimplantation development. Dev Biol. 1994;162(2):402-13.
      25. Motoyama J, Liu J, Mo R, Ding Q, Post M, Hui CC. Essential function of Gli2 and Gli3 in the formation of lung, trachea and oesophagus. Nat Genet. 1998;20(1):54-7.
      26. Chapman DL, Garvey N, Hancock S, Alexiou M, Agulnik SI, Gibson-Brown JJ, et al. Expression of the T-box family genes, Tbx1-Tbx5, during early mouse development. Dev Dyn. 1996;206(4):379-90.
      27. Kim HJ, Bar-Sagi D. Modulation of signalling by Sprouty: a developing story. Nat Rev Mol Cell Biol. 2004;5(6):441-50.
      28. Bellusci S, Furuta Y, Rush MG, Henderson R, Winnier G, Hogan BL. Involvement of Sonic hedgehog (Shh) in mouse embryonic lung growth and morphogenesis. Development. 1997;124(1):53-63.
      29. Zakin LD, Mazan S, Maury M, Martin N, Guénet JL, Brûlet P. Structure and expression of Wnt13, a novel mouse Wnt2 related gene. Mech Dev. 1998;73(1):107-16.
      30. Nelson WJ, Nusse R. Convergence of Wnt, beta-catenin, and cadherin pathways. Science. 2004;303(5663):1483-7.
      31. Okubo T, Hogan BL. Hyperactive Wnt signaling changes the developmental potential of embryonic lung endoderm. J Biol. 2004;3(3):11.
      32. Dean CH, Miller LA, Smith AN, Dufort D, Lang RA, Niswander LA. Canonical Wnt signaling negatively regulates branching morphogenesis of the lung and lacrimal gland. Dev Biol. 2005;286(1):270-86.
      33. De Langhe SP, Sala FG, Del Moral PM, Fairbanks TJ, Yamada KM, Warburton D, et al. Dickkopf-1 (DKK1) reveals that fibronectin is a major target of Wnt signaling in branching morphogenesis of the mouse embryonic lung. Dev Biol. 2005;277(2):316-31.
      34. Esni F, Ghosh B, Biankin AV, Lin JW, Albert MA, Yu X, et al. Notch inhibits Ptf1 function and acinar cell differentiation in developing mouse and zebrafish pancreas. Development. 2004;131(17):4213-24.
      35. Hald J, Hjorth JP, German MS, Madsen OD, Serup P, Jensen J. Activated Notch1 prevents differentiation of pancreatic acinar cells and attenuate endocrine development. Dev Biol. 2003;260(2):426-37.
      36. Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science. 1999;284(5415):770-6.
      37. Itoh K, Antipova A, Ratcliffe MJ, Sokol S. Interaction of dishevelled and Xenopus axin-related protein is required for wnt signal transduction. Mol Cell Biol. 2000;20(6):2228-38.
      38. Post LC, Ternet M, Hogan BL. Notch/Delta expression in the developing mouse lung. Mech Dev. 2000 Nov;98(1-2):95-8.
      39. Rizzo P, Osipo C, Foreman K, Golde T, Osborne B, Miele L. Rational targeting of Notch signaling in cancer. Oncogene. 2008;27(38):5124-31.
      40. Roy M, Pear WS, Aster JC. The multifaceted role of Notch in cancer. Curr Opin Genet Dev. 2007;17(1):52-9.
      41. Reedijk M, Odorcic S, Chang L, Zhang H, Miller N, McCready DR, et al. High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival. Cancer Res. 2005;65(18):8530-7.
      42. Pinnix CC, Herlyn M. The many faces of Notch signaling in skinderived cells. Pigment Cell Res. 2007;20(6):458-65.
      43. Nicolas M, Wolfer A, Raj K, Kummer JA, Mill P, van Noort M, et al. Notch1 functions as a tumor suppressor in mouse skin. Nat Genet. 2003;33(3):416-21.
      44. Koch U, Radtke F. Notch and cancer: a double-edged sword. Cell Mol Life Sci. 2007;64(21):2746-62.
      45. Tsao PN, Chen F, Izvolsky KI, Walker J, Kukuruzinska MA, Lu J, et al. Gamma-secretase activation of notch signaling regulates the balance of proximal and distal fates in progenitor cells of the developing lung. J Biol Chem. 2008;283(43):29532-44.
      46. Chen Y, De Marco MA, Graziani I, Gazdar AF, Strack PR, Miele L, et al. Oxygen concentration determines the biological effects of NOTCH-1 signaling in adenocarcinoma of the lung. Cancer Res. 2007;67(17):7954-9.
      47. Konishi J, Kawaguchi KS, Vo H, Haruki N, Gonzalez A, Carbone DP, et al. Gamma-secretase inhibitor prevents Notch3 activation and reduces proliferation in human lung cancers. Cancer Res. 2007;67(17):8051-7.
      48. Dang TP, Gazdar AF, Virmani AK, Sepetavec T, Hande KR, Minna JD, et al. Chromosome 19 translocation, overexpression of Notch3, and human lung cancer. J Natl Cancer Inst. 2000;92(16):1355-7.
      49. Weijzen S, Rizzo P, Braid M, Vaishnav R, Jonkheer SM, Zlobin A, et al. Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells. Nat Med. 2002;8(9):979-86.
      50. Zheng Q, Qin H, Zhang H, Li J, Hou L, Wang H, et al. Notch signaling inhibits growth of the human lung adenocarcinoma cell line A549. Oncol Rep. 2007;17(4):847-52.
      51. Dou GR, Wang YC, Hu XB, Hou LH, Wang CM, Xu JF, et al. RBPJ, the transcription factor downstream of Notch receptors, is essential for the maintenance of vascular homeostasis in adult mice. FASEB J. 2008;22(5):1606-17.
      52. Mailhos C, Modlich U, Lewis J, Harris A, Bicknell R, Ish-Horowicz D. Delta4, an endothelial specific notch ligand expressed at sites of physiological and tumor angiogenesis. Differentiation. 2001;69(2-3):135-44.
      53. Patel NS, Li JL, Generali D, Poulsom R, Cranston DW, Harris AL. Up-regulation of delta-like 4 ligand in human tumor vasculature and the role of basal expression in endothelial cell function. Cancer Res. 2005;65(19):8690-7.
      54. Noguera-Troise I, Daly C, Papadopoulos NJ, Coetzee S, Boland P, Gale NW, et al. Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Nature. 2006;444(7122):1032-7.
      55. Sahlgren C, Gustafsson MV, Jin S, Poellinger L, Lendahl U. Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci USA. 2008;105(17):6392-7.
      56. Timmerman LA, Grego-Bessa J, Raya A, Bertrán E, Pérez-Pomares JM, Díez J, et al. Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev. 2004;18(1):99-115.
      57. Pao W, Ladanyi M, Miller VA; Lung Cancer Oncogenome Group. Erlotinib in lung cancer. N Engl J Med. 2005;353(16):1739-41; author reply 1739-1741.
      58. Einhorn LH, Bonomi P, Bunn PA Jr, Camidge DR, Carbone DP, Choy H, et al. Summary report 7th Annual Targeted Therapies of the Treatment of Lung Cancer. J Thorac Oncol. 2008;3(5):545- 55.
      59. Ingham PW, McMahon AP. Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 2001;15(23):3059-87.
      60. Ogden SK, Ascano M Jr, Stegman MA, Robbins DJ. Regulation of Hedgehog signaling: a complex story. Biochem Pharmacol. 2004;67(5):805-14.
      61. Pepinsky RB, Rayhorn P, Day ES, Dergay A, Williams KP, Galdes A, et al. Mapping sonic hedgehog-receptor interactions by steric interference. J Biol Chem. 2000;275(15):10995-1001.
      62. Berman DM, Karhadkar SS, Hallahan AR, Pritchard JI, Eberhart CG, Watkins DN, et al. Medulloblastoma growth inhibition by hedgehog pathway blockade. Science. 2002;297(5586):1559-61.
      63. Thayer SP, di Magliano MP, Heiser PW, Nielsen CM, Roberts DJ, Lauwers GY, et al. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature. 2003;425(6960):851-6.
      64. Fan L, Pepicelli CV, Dibble CC, Catbagan W, Zarycki JL, Laciak R, et al. Hedgehog signaling promotes prostate xenograft tumor growth. Endocrinology. 2004;145(8):3961-70.
      65. Kubo M, Nakamura M, Tasaki A, Yamanaka N, Nakashima H, Nomura M, et al. Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Res 2004;64(17):6071-4.
      66. Watkins DN, Berman DM, Burkholder SG, Wang B, Beachy PA, Baylin SB. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature. 2003;422(6929):313-7.
      67. Lum L, Beachy PA. The Hedgehog response network: sensors, switches, and routers. Science. 2004;304(5678):1755-9.
      68. Toftgard R. Hedgehog signalling in cancer. Cell Mol Life Sci. 2000;57(12):1720-31.
      69. Reynolds SD, Hong KU, Giangreco A, Mango GW, Guron C, Morimoto Y, et al. Conditional clara cell ablation reveals a self-renewing progenitor function of pulmonary neuroendocrine cells. Am J Physiol Lung Cell Mol Physiol. 2000;278(6):L1256-63.
      70. Fujita E, Khoroku Y, Urase K, Tsukahara T, Momoi MY, Kumagai H, et al. Involvement of Sonic hedgehog in the cell growth of LK-2 cells, human lung squamous carcinoma cells. Biochem Biophys Res Commun. 1997;238(2):658-64.
      71. Yuan Z, Goetz JA, Singh S, Ogden SK, Petty WJ, Black CC, et al. Frequent requirement of hedgehog signaling in non-small cell lung carcinoma. Oncogene. 2007;26(7):1046-55.
      72. Nusse R, Varmus HE. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell. 1982;31(1):99-109.
      73. Yamaguchi TP, Bradley A, McMahon AP, Jones S. Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development. 1999;126(6):1211-23.
      74. Weidenfeld J, Shu W, Zhang L, Millar SE, Morrisey EE. The WNT7b promoter is regulated by TTF-1, GATA6, and Foxa2 in lung epithelium. J Biol Chem. 2002;277(23):21061-70.
      75. Li C, Xiao J, Hormi K, Borok Z, Minoo P. Wnt5a participates in distal lung morphogenesis. Dev Biol. 2002;248(1):68-81.
      76. Chilosi M, Poletti V, Zamo A, Lestani M, Montagna L, Piccoli P, et al. Aberrant Wnt/beta-catenin pathway activation in idiopathic pulmonary fibrosis. Am J Pathol. 2003;162(5):1495-502.
      77. Zeng X, Tamai K, Doble B, Li S, Huang H, Habas R, et al. A dualkinase mechanism for Wnt co-receptor phosphorylation and activation. Nature. 2005;438(7069):873-7.
      78. Moreno-Bueno G, Hardisson D, Sánchez C, Sarrio D, Cassia R, García-Rostán G, et al. Abnormalities of the APC/ beta-catenin pathway in endometrial cancer. Oncogene. 2002;21(52):7981-90.
      79. Gerstein AV, Almeida TA, Zhao G, Chess E, Shih IeM, Buhler K, et al. APC/CTNNB1 (beta-catenin) pathway alterations in human prostate cancers. Genes Chromosomes Cancer. 2002;34(1):9-16.
      80. Howe LR, Brown AM. Wnt signaling and breast cancer. Cancer Biol Ther. 2004;3(1):36-41.
      81. de La Coste A, Romagnolo B, Billuart P, Renard CA, Buendia MA, Soubrane O, et al. Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas. Proc Natl Acad Sci USA. 1998;95(15):8847-51.
      82. He B, You L, Uematsu K, Xu Z, Lee AY, Matsangou M, et al. A monoclonal antibody against Wnt-1 induces apoptosis in human cancer cells. Neoplasia. 2004;6(1):7-14.
      83. You L, He B, Xu Z, Uematsu K, Mazieres J, Mikami I, et al. Inhibition of Wnt-2-mediated signaling induces programmed cell death in non-small-cell lung cancer cells. Oncogene. 2004;23(36):6170-4.
      84. Mazieres J, He B, You L, Xu Z, Lee AY, Mikami I, et al. Wnt inhibitory factor-1 is silenced by promoter hypermethylation in human lung cancer. Cancer Res. 2004;64(14):4717-20.
      85. Kim J, You L, Xu Z, Kuchenbecker K, Raz D, He B, et al. Wnt inhibitory factor inhibits lung cancer cell growth. J Thorac Cardiovasc Surg. 2007;133(3):733-7.
      86. Yue W, Sun Q, Dacic S, Landreneau RJ, Siegfried JM, Yu J, et al. Downregulation of Dkk3 activates beta-catenin/TCF-4 signaling in lung cancer. Carcinogenesis. 2008;29(1):84-92.
      87. You L, He B, Uematsu K, Xu Z, Mazieres J, Lee A, et al. Inhibition of Wnt-1 signaling induces apoptosis in beta-catenin-deficient mesothelioma cells. Cancer Res. 2004;64(10):3474-8.
      88. Nakashima T, Liu D, Nakano J, Ishikawa S, Yokomise H, Ueno M, et al. Wnt1 overexpression associated with tumor proliferation and a poor prognosis in non-small cell lung cancer patients. Oncol Rep. 2008;19(1):203-9.
      89. Ohira T, Gemmill RM, Ferguson K, Kusy S, Roche J, Brambilla E, et al. WNT7a induces E-cadherin in lung cancer cells. Proc Natl Acad Sci USA. 2003;100(18):10429-34.
      90. Uematsu K, He B, You L, Xu Z, McCormick F, Jablons DM. Activation of the Wnt pathway in non small cell lung cancer: evidence of dishevelled overexpression. Oncogene. 2003;22(46):7218- 21.
      91. Uematsu K, Kanazawa S, You L, He B, Xu Z, Li K, et al. Wnt pathway activation in mesothelioma: evidence of Dishevelled overexpression and transcriptional activity of beta-catenin. Cancer Res. 2003;63(15):4547-51.
      92. Wei Q, Zhao Y, Yang ZQ, Dong QZ, Dong XJ, Han Y, et al. Dishevelled family proteins are expressed in non-small cell lung cancer and function differentially on tumor progression. Lung Cancer. 2008;62(2):181-92.
      93. Sunaga N, Kohno T, Kolligs FT, Fearon ER, Saito R, Yokota J. Constitutive activation of the Wnt signaling pathway by CTNNB1 (beta-catenin) mutations in a subset of human lung adenocarcinoma. Genes Chromosom Cancer. 2001;30(3):316-21.
      94. Ohgaki H, Kros JM, Okamoto Y, Gaspert A, Huang H, Kurrer MO. APC mutations are infrequent but present in human lung cancer. Cancer Lett. 2004;207(2):197-203.
      95. Kase S, Sugio K, Yamazaki K, Okamoto T, Yano T, Sugimachi K. Expression of E-cadherin and beta-catenin in human non-small cell lung cancer and the clinical significance. Clin Cancer Res. 2000;6(12):4789-96.
      96. Suzuki M, Shigematsu H, Nakajima T, Kubo R, Motohashi S, Sekine Y, et al. Synchronous alterations of Wnt and epidermal growth factor receptor signaling pathways through aberrant methylation and mutation in non small cell lung cancer. Clin Cancer Res. 2007;13(20):6087-92.
      97. Batra S, Shi Y, Kuchenbecker KM, He B, Reguart N, Mikami I, et al. Wnt inhibitory factor-1, a Wnt antagonist, is silenced by promoter hypermethylation in malignant pleural mesothelioma. Biochem Biophys Res Commun. 2006;342(4):1228-32.
      98. Lee AY, He B, You L, Dadfarmay S, Xu Z, Mazieres J, et al. Expression of the secreted frizzled-related protein gene family is downregulated in human mesothelioma. Oncogene. 2004;23(39):6672-6.
      99. Tsuji T, Miyazaki M, Sakaguchi M, Inoue Y, Namba MA. A REIC gene shows down-regulation in human immortalized cells and human tumor-derived cell lines. Biochem Biophys Res Commun. 2000;268(1):20-4.
      100. Collins BJ, Kleeberger W, Ball DW. Notch in lung development and lung cancer. Semin Cancer Biol. 2004;14(5):357-64.
      101. Aguayo AJ, Bray GM, Rasminsky M, Zwimpfer T, Carter D, Vidal-Sanz M. Synaptic connections made by axons regenerating in the central nervous system of adult mammals. J Exp Biol. 1990;153:199-224.
      102. Bianchi L, Driscoll M. Heterologous expression of C. elegans ion channels in Xenopus oocytes. WormBook. 2006:1-16.
      103. Shan L, Aster JC, Sklar J, Sunday ME. Notch-1 regulates pulmonary neuroendocrine cell differentiation in cell lines and in transgenic mice. Am J Physiol Lung Cell Mol Physiol. 2007;292(2):L500-9.
      104. Greenblatt DY, Vaccaro AM, Jaskula-Sztul R, Ning L, Haymart M, Kunnimalaiyaan M, et al. Valproic acid activates notch-1 signaling and regulates the neuroendocrine phenotype in carcinoid cancer cells. Oncologist. 2007;12(8):942-51.
      105. Sriuranpong V, Borges MW, Strock CL, Nakakura EK, Watkins DN, Blaumueller CM, et al. Notch signaling induces rapid degradation of achaete-scute homolog 1. Mol Cell Biol. 2002;22(9):3129-39.
      106. Lee J, Platt KA, Censullo P, Ruiz i Altaba A. Gli1 is a target of Sonic hedgehog that induces ventral neural tube development. Development. 1997;124(13):2537-52.
      107. Taipale J, Chen JK, Cooper MK, Wang B, Mann RK, Milenkovic L, et al. Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine. Nature. 2000;406(6799):1005-9.
      108. Ericson J, Morton S, Kawakami A, Roelink H, Jessell TM. Two critical periods of Sonic Hedgehog signaling required for the specification of motor neuron identity. Cell. 1996;87(4):661- 73.
      109. Vestergaard J, Pedersen MW, Pedersen N, Ensinger C, Tümer Z, Tommerup N, et al. Hedgehog signaling in small-cell lung cancer: frequent in vivo but a rare event in vitro. Lung Cancer. 2006;52(3):281-90.
      110. Weaver M, Yingling JM, Dunn NR, Bellusci S, Hogan BL. Bmp signaling regulates proximal-distal differentiation of endoderm in mouse lung development. Development. 1999;126(18):4005-15.
      111. Pasca di Magliano M, Hebrok M. Hedgehog signalling in cancer formation and maintenance. Nat Rev Cancer. 2003;3(12):903-11.
      112. Barnes EA, Kong M, Ollendorff V, Donoghue DJ. Patched1 interacts with cyclin B1 to regulate cell cycle progression. EMBO J. 2001;20(9):2214-23.
      113. Ohta M, Tateishi K, Kanai F, Watabe H, Kondo S, Guleng B, et al. p53-Independent negative regulation of p21/cyclin-de pendent kinase-interacting protein 1 by the sonic hedgehogglioma-associated oncogene 1 pathway in gastric carcinoma cells. Cancer Res. 2005;65(23):10822-9.
      114. Fan H, Khavari PA. Sonic hedgehog opposes epithelial cell cycle arrest. J Cell Biol. 1999;147(1):71-6.
      115. Yoshinori A, Tobiume K. The negative regulation of p53 by hedgehog signaling. AACR. 2006. Abstract 1135-b.
      116. Olsen CL, Hsu PP, Glienke J, Rubanyi GM, Brooks AR. Hedgehog-interacting protein is highly expressed in endothelial cells but down-regulated during angiogenesis and in several human tumors. BMC Cancer. 2004;4:43.
      117. Kanda S, Mochizuki Y, Suematsu T, Miyata Y, Nomata K, Kanetake H. Sonic hedgehog induces capillary morphogenesis by endothelial cells through phosphoinositide 3-kinase. J Biol Chem. 2003;278(10):8244-9.
      118. Osada H, Tatematsu Y, Yatabe Y, Horio Y, Takahashi T. ASH1 gene is a specific therapeutic target for lung cancers with neuroendocrine features. Cancer Res. 2005;65(23):10680-5.
      119. Linnoila RI, Zhao B, DeMayo JL, Nelkin BD, Baylin SB, DeMayo FJ, et al. Constitutive achaete-scute homologue-1 promotes airway dysplasia and lung neuroendocrine tumors in transgenic mice. Cancer Res. 2000;60(15):4005-9.
      120. Salon C, Moro D, Lantuejoul S, Brichon Py P, Drabkin H, Brambilla C, et al. E-cadherin-beta-catenin adhesion complex in neuroendocrine tumors of the lung: a suggested role upon local invasion and metastasis. Hum Pathol. 2004;35(9):1148-55.
      121. Pelosi G, Scarpa A, Puppa G, Veronesi G, Spaggiari L, Pasini F, et al. Alteration of the E-cadherin/beta-catenin cell adhesion system is common in pulmonary neuroendocrine tumors and is an independent predictor of lymph node metastasis in atypical carcinoids. Cancer. 2005;103(6):1154-64.

      Información

      Directorios e indexadores
      Perfil de Google Scholar

      Código QR

      Palabras clave

      Más leídos en los últimos 30 días

      Número actual

      Sistema OJS 3.4.0.7 - Metabiblioteca |