OpenLB
Open Library of Bioscience
Advanced Search
Frontiers in bioscience (Landmark edition)
01 01, 2012;17 (1): 90-9.

Cooperative Hedgehog-EGFR signaling.

Doris Mangelberger, Daniela Kern, Andrea Loipetzberger, Markus Eberl, Fritz Aberger
Author Information
  1. Doris Mangelberger: Division of Molecular Tumor Biology, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
PMID: 22201734 DOI: 10.2741/3917

Abstract

It has been known for many years that cooperative interactions between oncogenes (e.g. RAS, MYC, BCL2) can fuel cancer growth (1-5), but the restricted druggability of many of those interacting cancer genes has hampered translation of combined targeting to medical cancer therapy. The identification and characterization of cooperative cancer signaling pathways amenable to medical therapy is therefore a crucial step towards the establishment of efficient targeted combination treatments urgently needed to improve cancer therapy. Here we review recent findings of our group and colleagues on the molecular mechanisms of cooperative Hedgehog/GLI and Epidermal Growth Factor Receptor (EGFR) signaling, two clinically relevant oncogenic pathways involved in the development of many human malignancies. We also discuss the possible implications of these findings for the design of a therapeutic regimen relying on combined targeting of key effectors of both pathways.

References

  1. Science. 2009 Jun 12;324(5933):1457-61 [PMID: 19460966]
  2. Sci Transl Med. 2010 Sep 29;2(51):51ra70 [PMID: 20881279]
  3. Development. 2010 Jul;137(13):2079-94 [PMID: 20530542]
  4. Cell Cycle. 2007 Oct 15;6(20):2458-63 [PMID: 17726373]
  5. Int J Cancer. 2006 Feb 15;118(4):1022-31 [PMID: 16108016]
  6. Cell. 2000 Jan 7;100(1):57-70 [PMID: 10647931]
  7. Genes Dev. 2009 Jan 1;23(1):24-36 [PMID: 19136624]
  8. Nature. 1983 Aug 18-24;304(5927):602-6 [PMID: 6308473]
  9. Science. 2009 Oct 23;326(5952):572-4 [PMID: 19726788]
  10. Dermatol Clin. 1995 Jan;13(1):113-25 [PMID: 7712637]
  11. Science. 1987 Apr 3;236(4797):70-3 [PMID: 3563490]
  12. Oncogene. 2005 Jun 16;24(26):4232-42 [PMID: 15824737]
  13. Nature. 2007 Mar 8;446(7132):153-8 [PMID: 17344846]
  14. Mol Carcinog. 2009 Aug;48(8):703-12 [PMID: 19142899]
  15. Nat Cell Biol. 2007 Sep;9(9):1005-9 [PMID: 17762891]
  16. N Engl J Med. 2009 Sep 17;361(12):1173-8 [PMID: 19726761]
  17. Genomics. 2009 Jan;93(1):17-21 [PMID: 18692126]
  18. Cell. 1996 Jun 14;85(6):841-51 [PMID: 8681379]
  19. J Invest Dermatol. 2004 Jun;122(6):1503-9 [PMID: 15175043]
  20. Nat Rev Cancer. 2002 May;2(5):361-72 [PMID: 12044012]
  21. Cancer Cell. 2008 Sep 9;14(3):238-49 [PMID: 18772113]
  22. Nat Rev Cancer. 2005 May;5(5):341-54 [PMID: 15864276]
  23. PLoS Med. 2005 Nov;2(11):e313 [PMID: 16187797]
  24. Nature. 2004 Nov 18;432(7015):324-31 [PMID: 15549094]
  25. Curr Biol. 2007 Jan 23;17(2):165-72 [PMID: 17196391]
  26. Nat Rev Cancer. 2008 Oct;8(10):743-54 [PMID: 18813320]
  27. Curr Opin Cell Biol. 1999 Apr;11(2):184-9 [PMID: 10209149]
  28. Mol Cancer. 2009 Jun 25;8:40 [PMID: 19555497]
  29. PLoS Comput Biol. 2010 Aug 26;6(8): [PMID: 20865152]
  30. Nat Rev Mol Cell Biol. 2001 Feb;2(2):127-37 [PMID: 11252954]
  31. Nature. 1983 Aug 18-24;304(5927):596-602 [PMID: 6308472]
  32. Development. 2005 Jan;132(2):335-44 [PMID: 15604099]
  33. Nature. 1980 Oct 30;287(5785):795-801 [PMID: 6776413]
  34. Nature. 1998 Jan 1;391(6662):90-2 [PMID: 9422511]
  35. Nat Med. 2004 Aug;10(8):789-99 [PMID: 15286780]
  36. Mol Cancer Ther. 2007 Mar;6(3):967-78 [PMID: 17363490]
  37. Science. 2006 Oct 13;314(5797):268-74 [PMID: 16959974]
  38. Mol Cell Biol. 2006 Aug;26(16):6283-98 [PMID: 16880536]
  39. Genes Dev. 2010 Sep 15;24(18):2001-12 [PMID: 20844013]
  40. Nat Med. 2007 Aug;13(8):944-51 [PMID: 17632527]
  41. Cell. 2000 Oct 13;103(2):211-25 [PMID: 11057895]
  42. Nat Rev Cancer. 2003 Dec;3(12):903-11 [PMID: 14737121]
  43. J Clin Oncol. 2005 Apr 10;23(11):2513-20 [PMID: 15738541]
  44. Nature. 2009 Apr 9;458(7239):776-9 [PMID: 19169242]
  45. Eur J Cancer. 2006 Mar;42(4):437-45 [PMID: 16406505]
  46. Cancer Res. 2006 Jan 15;66(2):839-45 [PMID: 16424016]
  47. Nat Genet. 2007 Mar;39(3):347-51 [PMID: 17293865]
  48. Oncogene. 2009 Apr 2;28(13):1639-51 [PMID: 19219074]
  49. Cancer Res. 2009 Feb 15;69(4):1284-92 [PMID: 19190345]
  50. Science. 2004 Jun 4;304(5676):1497-500 [PMID: 15118125]
  51. Nature. 2008 Sep 18;455(7211):406-10 [PMID: 18754008]
  52. J Cell Sci. 2007 Jan 1;120(Pt 1):3-6 [PMID: 17182898]
  53. Science. 2007 Jul 20;317(5836):372-6 [PMID: 17641202]
  54. Biochim Biophys Acta. 2010 Apr;1805(2):181-208 [PMID: 20085802]
  55. J Clin Oncol. 2010 Jul 10;28(20):3366-79 [PMID: 20530283]
  56. Medicine (Baltimore). 1987 Mar;66(2):98-113 [PMID: 3547011]
  57. Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4505-10 [PMID: 16537363]
  58. Trends Cell Biol. 2007 Sep;17(9):438-47 [PMID: 17845852]
  59. Cell Cycle. 2006 Aug;5(15):1612-5 [PMID: 16880744]
  60. J Mol Cell Biol. 2010 Apr;2(2):84-95 [PMID: 20083481]
  61. Nat Struct Mol Biol. 2010 Jun;17(6):718-25 [PMID: 20512148]
  62. J Invest Dermatol. 2005 Feb;124(2):457-65 [PMID: 15675968]
  63. Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5895-900 [PMID: 17392427]
  64. Dev Cell. 2008 Dec;15(6):801-12 [PMID: 19081070]
  65. Nat Med. 2009 Sep;15(9):1055-61 [PMID: 19701205]
  66. Differentiation. 2007 Nov;75(9):770-87 [PMID: 17999740]
  67. N Engl J Med. 2009 Sep 17;361(12):1164-72 [PMID: 19726763]
  68. Trends Pharmacol Sci. 2009 Jun;30(6):303-12 [PMID: 19443052]
  69. N Engl J Med. 2004 May 20;350(21):2129-39 [PMID: 15118073]
  70. Genes Dev. 2001 Dec 1;15(23):3059-87 [PMID: 11731473]
  71. Cancer Res. 2007 Feb 1;67(3):1030-7 [PMID: 17283135]
  72. EMBO Mol Med. 2009 Sep;1(6-7):338-51 [PMID: 20049737]
  73. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3196-201 [PMID: 19218434]
  74. Gastroenterology. 2009 Sep;137(3):1102-13 [PMID: 19501590]
  75. Science. 1996 Jun 14;272(5268):1668-71 [PMID: 8658145]
  76. Science. 2007 Nov 16;318(5853):1108-13 [PMID: 17932254]
  77. FEBS Lett. 2010 Jun 18;584(12):2699-706 [PMID: 20388509]
  78. Nat Genet. 2002 Jul;31(3):306-10 [PMID: 12068298]
  79. Nature. 2008 Jun 19;453(7198):1112-6 [PMID: 18500333]
  80. Nature. 1990 Nov 22;348(6299):331-3 [PMID: 2250704]
  81. Development. 2004 Jan;131(2):337-45 [PMID: 14681189]

Grants

  1. P 20652/Austrian Science Fund FWF

MeSH Term

ErbB Receptors
Hedgehog Proteins
Humans
MAP Kinase Signaling System
Models, Biological
Neoplasms
Signal Transduction
Transcription Factors
Zinc Finger Protein GLI1

Chemicals

GLI1 protein, human
Hedgehog Proteins
Transcription Factors
Zinc Finger Protein GLI1
ErbB Receptors
Journal Article Research Support, Non-U.S. Gov't Review

Word Cloud

Created with Highcharts 10.0.0cancermanycooperativetherapysignalingpathwayscombinedtargetingmedicalfindingsknownyearsinteractionsoncogenesegRASMYCBCL2canfuelgrowth1-5restricteddruggabilityinteractinggeneshamperedtranslationidentificationcharacterizationamenablethereforecrucialsteptowardsestablishmentefficienttargetedcombinationtreatmentsurgentlyneededimprovereviewrecentgroupcolleaguesmolecularmechanismsHedgehog/GLIEpidermalGrowthFactorReceptorEGFRtwoclinicallyrelevantoncogenicinvolveddevelopmenthumanmalignanciesalsodiscusspossibleimplicationsdesigntherapeuticregimenrelyingkeyeffectorsCooperativeHedgehog-EGFR

Similar Articles

Cited By