Expression of Bmi1, FoxF1, Nanog, and γ-Catenin in Relation to Hedgehog Signaling Pathway in Human Non-small-Cell Lung Cancer
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  • 作者:Ioannis P. Gialmanidis ; Vasiliki Bravou ; Ilias Petrou ; Helen Kourea…
  • 关键词:Bmi1 ; FoxF1 ; Hedgehog ; Nanog ; NSCLC
  • 刊名:Lung
  • 出版年:2013
  • 出版时间:October 2013
  • 年:2013
  • 卷:191
  • 期:5
  • 页码:511-521
  • 全文大小:866KB
  • 参考文献:1. Daniel VC, Peacock CD, Watkins DN (2006) Developmental signalling pathways in lung cancer. Respirology 11(3):234-40 CrossRef
    2. van Tuyl M, Post M (2000) From fruitflies to mammals: mechanisms of signalling via the Sonic hedgehog pathway in lung development. Respir Res 1(1):30-5 CrossRef
    3. Velcheti V, Govindan R (2007) Hedgehog signaling pathway and lung cancer. J Thorac Oncol 2(1):7-0 CrossRef
    4. Ruiz i Altaba A, Stecca B, Sánchez P, Ruiz i Altaba A, Stecca B, Sánchez P (2004) Hedgehog–Gli signaling in brain tumors: stem cells and paradevelopmental programs in cancer. Cancer Lett 204(2):145-57 CrossRef
    5. Kalderon D (2000) Transducing the hedgehog signal. Cell 103(3):371-74 CrossRef
    6. Mullor JL, Sánchez P, Ruiz i Altaba A (2002) Pathways and consequences: hedgehog signaling in human disease. Trends Cell Biol 12(12):562-69 CrossRef
    7. Gialmanidis IP, Bravou V, Amanetopoulou SG et al (2009) Overexpression of hedgehog pathway molecules and FOXM1 in non-small cell lung carcinomas. Lung Cancer. 66(1):64-4 CrossRef
    8. Michael LE, Westerman BA, Ermilov AN et al (2008) Bmi1 is required for Hedgehog pathway-driven medulloblastoma expansion. Neoplasia 10(12):1343-349
    9. Zbinden M, Duquet A, Lorente-Trigos A et al (2010) NANOG regulates glioma stem cells and is essential in vivo acting in a cross-functional network with GLI1 and p53. EMBO J 29(15):2659-674 mboj.2010.137">CrossRef
    10. Yoon JW, Kita Y, Frank DJ et al (2002) Gene expression profiling leads to identification of GLI1-binding elements in target genes and a role for multiple downstream pathways in GLI1-induced cell transformation. J Biol Chem 277(7):5548-555 CrossRef
    11. Jacobs JJ, Kieboom K, Marino S et al (1999) The oncogene and Polycomb-group gene / bmi- / 1 regulates cell proliferation and senescence through the ink4a locus. Nature 397(6715):164-68 CrossRef
    12. Park IK, Qian D, Kiel M et al (2003) Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423(6937):302-05 CrossRef
    13. Molofsky AV, Pardal R, Iwashita T et al (2003) Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 425(6961):962-67 CrossRef
    14. Molofsky AV, He S, Bydon M et al (2005) Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways. Genes Dev 19(12):1432-437 CrossRef
    15. Prince ME, Sivanandan R, Kaczorowski A et al (2007) Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci U S A 104(3):973-78 CrossRef
    16. Liu JH, Song LB, Zhang X et al (2008) / Bmi- / 1 expression predicts prognosis for patients with gastric carcinoma. J Surg Oncol 97(3):267-72 CrossRef
    17. Vonlanthen S, Heighway J, Altermatt HJ et al (2001) The bmi-1 oncoprotein is differentially expressed in non-small cell lung cancer and correlates with INK4A-ARF locus expression. Br J Cancer 84(10):1372-376 CrossRef
    18. Kaufmann E, Kn?chel W (1996) Five years on the wings of fork head. Mech Dev 57(1):3-0 CrossRef
    19. Stankiewicz P, Sen P, Bhatt SS et al (2009) Genomic and genic deletions of the FOX gene cluster on 16q24.1 and inactivating mutations of FOXF1 cause alveolar capillary dysplasia and other malformations. Am J Hum Genet 84(6):780-91 CrossRef
    20. Yamaguchi S, Kimura H, Tada M et al (2005) Nanog expression in mouse germ cell development. Gene Expr Patterns 5(5):639-46 modgep.2005.03.001">CrossRef
    21. Chiou SH, Wang ML, Chou YT et al (2010) Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. Cancer Res 70(24):10433-0444 CrossRef
    22. Barker N, Clevers H (2000) Catenins. Wnt signaling and cancer. Bioessays 22(11):961-65 CrossRef
    23. Wendling DS, Lück C, von Schweinitz D et al (2008) Characteristic overexpression of the forkhead box transcription factor Foxf1 in Patched-associated tumors. Int J Mol Med 22(6):787-92
    24. Dlugosz AA, Talpaz M (2009) Following the hedgehog to new cancer therapies. N Engl J Med 361(12):1202-205 CrossRef
    25. Xu F, Yang R, Wu L et al (2012) Overexpression of BMI1 confers clonal cells resistance to apoptosis and contributes to adverse prognosis in myelodysplastic syndrome. Cancer Lett 317(1):33-0 CrossRef
    26. Lo PK, Lee JS, Liang X et al (2010) Epigenetic inactivation of the potential tumor suppressor gene FOXF1 in breast cancer. Cancer Res 70(14):6047-058 CrossRef
    27. Saito RA, Micke P, Paulsson J et al (2010) Forkhead box F1 regulates tumor-promoting properties of cancer-associated fibroblasts in lung cancer. Cancer Res 70(7):2644-654 CrossRef
    28. Maeda Y, Davé V, Whitsett JA (2007) Transcriptional control of lung morphogenesis. Physiol Rev 87(1):219-44 CrossRef
    29. Shakhova O, Leung C, Marino S (2005) Bmi1 in development and tumorigenesis of the central nervous system. J Mol Med 83(8):596-00 CrossRef
    30. Grinstein E, Mahotka C (2009) Stem cell divisions controlled by the proto-oncogene BMI-1. J Stem Cells 4(3):141-46
    31. Kalinichenko VV, Gusarova GA, Kim IM et al (2004) Foxf1 haploinsufficiency reduces Notch-2 signaling during mouse lung development. Am J Physiol Lung Cell Mol Physiol 286(3):L521–L530 CrossRef
    32. Mahlapuu M, Enerb?ck S, Carlsson P (2001) Haploinsufficiency of the forkhead gene / Foxf1, a target for sonic hedgehog signaling, causes lung and foregut malformations. Development 128(12):2397-406
    33. Teglund S (1805) Toftg?rd R (2010) Hedgehog beyond medulloblastoma and basal cell carcinoma. Biochim Biophys Acta 2:181-08
    34. Liu S, Dontu G, Mantle ID et al (2006) Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res 66(12):6063-071 CrossRef
    35. Nirasawa S, Kobayashi D, Tsuji N et al (2009) Diagnostic relevance of overexpressed Nanog gene in early lung cancers. Oncol Rep 22(3):587-91
    36. Yuan P, Kadara H, Behrens C et al (2010) Sex determining region Y-Box 2 (SOX2) is a potential cell-lineage gene highly expressed in the pathogenesis of squamous cell carcinomas of the lung. PLoS ONE 5(2):e9112 CrossRef
    37. Leung EL, Fiscus RR, Tung JW et al (2010) Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties. PLoS ONE 5(11):e14062 CrossRef
    38. Forte A, Schettino MT, Finicelli M et al (2009) Expression pattern of stemness-related genes in human endometrial and endometriotic tissues. Mol Med 15(11-2):392-01
    39. Melone MA, Giuliano M, Squillaro T et al (2009) Genes involved in regulation of stem cell properties: studies on their expression in a small cohort of neuroblastoma patients. Cancer Biol Ther 8(13):1300-306 CrossRef
    40. Mathieu J, Zhang Z, Zhou W et al (2011) HIF induces human embryonic stem cell markers in cancer cells. Cancer Res 71(13):4640-652 CrossRef
    41. Aktary Z, Pasdar M (2012) Plakoglobin: role in tumorigenesis and metastasis. Int J Cell Biol 2012:189521
    42. Nagel JM, Kriegl L, Horst D et al (2010) γ-Catenin is an independent prognostic marker in early stage colorectal cancer. Int J Colorectal Dis 25(11):1301-309 CrossRef
    43. Shahi MH, Afzal M, Sinha S et al (2010) Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma. BMC Cancer 10:614 CrossRef
    44. Kolligs FT, Kolligs B, Hajra KM et al (2000) γ-Catenin is regulated by the APC tumor suppressor and its oncogenic activity is distinct from that of beta-catenin. Genes Dev 14(11):1319-331
    45. Chikaishi Y, Uramoto H, Tanaka F (2011) The EMT status in the primary tumor does not predict postoperative recurrence or disease-free survival in lung adenocarcinoma. Anticancer Res 31(12):4451-456
    46. Yamashita T, Uramoto H, Onitsuka T et al (2010) Association between lymphangiogenesis-/micrometastasis- and adhesion-related molecules in resected stage I NSCLC. Lung Cancer 70(3):320-28 CrossRef
    47. Winn RA, Bremnes RM, Bemis L et al (2002) γ-Catenin expression is reduced or absent in a subset of human lung cancers and re-expression inhibits transformed cell growth. Oncogene 21(49):7497-506 CrossRef
    48. Shahi MH, Schiapparelli P, Afzal M et al (2011) Expression and epigenetic modulation of sonic hedgehog-GLI1 pathway genes in neuroblastoma cell lines and tumors. Tumour Biol 32(1):113-27 CrossRef
  • 作者单位:Ioannis P. Gialmanidis (1)
    Vasiliki Bravou (1)
    Ilias Petrou (1)
    Helen Kourea (2)
    Alexandros Mathioudakis (3)
    Ioannis Lilis (1)
    Helen Papadaki (1)

    1. Department of Anatomy, School of Medicine, University of Patras, 26500, Rio Patras, Greece
    2. Department of Pathology, School of Medicine, University of Patras, 26500, Rio Patras, Greece
    3. Southport and Ormskirk Hospital NHS Trust, Southport, Merseyside, PR8 6PN, UK
  • ISSN:1432-1750
文摘
Background Hedgehog signaling is known to be involved in both lung organogenesis and lung carcinogenesis. The aim of this study was to examine potential downstream targets of the hedgehog signaling pathway in non-small-cell lung cancer. Methods Protein expression of Bmi1, FoxF1, Nanog, and γ-catenin was examined by immunohistochemistry in 80 non-small-cell lung cancer samples. Correlations with the previously immunohistochemically recovered results for sonic hedgehog, Ptch1, Smo, Gli1, and Gli2 in the same cohort of tumors as well as the clinicopathological characteristics of the tumors were also evaluated. Results Bmi1 was expressed in 78/80 (97.5?%) cases of non-small-cell lung cancer and correlated with male gender and expression of Gli1. Positive expression of FoxF1 was found in 62/80 (77.5?%) cases. Expression of FoxF1 correlated with lymph node metastases, Bmi1, and hedgehog pathway activation. Overexpression of Nanog was also noted in 74/80 (92.5?%) tumors and correlated with Bmi1. Cytoplasmic accumulation of γ-catenin was observed in 85?% (68/80) of the tumors and correlated with the expression of Bmi1, FoxF1, and Nanog. Conclusion Several developmental pathways seem to be implicated in non-small-cell lung cancer. It is also suggested that Bmi1 and FoxF1 may cooperate with hedgehog signaling in non-small-cell lung carcinogenesis.

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