Targeting γ-secretase in breast cancer

Breast Cancer: Targets and Therapy

Volumn 4, Issue , 2012, Pages 83-90

  Han, Jianxun ^a   Shen, Qiang ^b  

^a UNIVERSITY OF TORONTO   (Canada)

^b PRINCESS MARGARET HOSPITAL   (Canada)

Author keywords

Breast cancer; GSI; Notch; secretase

Indexed keywords

EID: 84924862734     PISSN: None     EISSN: 11791314     Source Type: Journal    
DOI: 10.2147/BCTT.S26437     Document Type: Review

References (83)

1. McCarthy JV, Twomey C, Wujek P. Presenilin-dependent regulated intramembrane proteolysis and gamma-secretase activity. Cell Mol Life Sci. 2009;66(9):1534-1555.
2. De Strooper B, Annaert W. Novel research horizons for presenilins and γ-secretases in cell biology and disease. Annu Rev Cell Dev Biol. 2010;26:235-260.
3. Jorissen E, De Strooper B. Gamma-secretase and the intramembrane proteolysis of Notch. Curr Top Dev Biol. 2010;92:201-230.
4. Gu Y, Chen F, Sanjo N, et al. APH-1 interacts with mature and immature forms of presenilins and nicastrin and may play a role in maturation of presenilin, nicastrin complexes. J Biol Chem. 2003;278(9): 7374-7380.
5. Lai MT, Chen E, Crouthamel MC, et al. Presenilin-1 and presenilin-2 exhibit distinct yet overlapping gamma-secretase activities. J Biol Chem. 2003;278(25):22475-22481.
6. Serneels L, Van Biervliet J, Craessaerts K, et al. Gamma-secretase heterogeneity in the Aph1 subunit: relevance for Alzheimer's disease. Science. 2009;324(5927):639-642.
7. Shah S, Lee SF, Tabuchi K, et al. Nicastrin functions as a gamma-secretase-substrate receptor. Cell. 2005;122(3):435-447.
8. Zhao G, Liu Z, Ilagan MX, Kopan R. Gamma-secretase composed of PS1/Pen2/Aph1a can cleave notch and amyloid precursor protein in the absence of nicastrin. J Neurosci. 2010;30(5):1648-1656.
9. Takasugi N, Tomita T, Hayashi I, et al. The role of presenilin cofactors in the gamma-secretase complex. Nature. 2003;422(6930):438-441.
10. Chen AC, Guo LY, Ostaszewski BL, Selkoe DJ, LaVoie MJ. Aph-1 associates directly with full-length and C-terminal fragments of gamma-secretase substrates. J Biol Chem. 2010;285(15):11378-11391.
11. Haass C, Steiner H. Alzheimer disease gamma-secretase: a complex story of GxGD-type presenilin proteases. Trends Cell Biol. 2002;12(12): 556-562.
12. Olson RE, Albright CF. Recent progress in the medicinal chemistry of gamma-secretase inhibitors. Curr Top Med Chem. 2008;8(1):17-33.
13. Kreft AF, Martone R, Porte A. Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease. J Med Chem. 2009;52(20):6169-6188.
14. Shearman MS, Beher D, Clarke EE, et al. L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid beta-protein precursor gamma-secretase activity. Biochemistry. 2000;39(30): 8698-8704.
15. Clarke EE, Churcher I, Ellis S, et al. Intra- or intercomplex binding to the gamma-secretase enzyme. A model to differentiate inhibitor classes. J Biol Chem. 2006;281(42):31279-31289.
16. Dovey HF, John V, Anderson JP, et al. Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J Neurochem. 2001;76(1):173-181.
17. Seiffert D, Bradley JD, Rominger CM, et al. Presenilin-1 and -2 are molecular targets for gamma-secretase inhibitors. J Biol Chem. 2000;275(44):34086-34091.
18. Wong GT, Manfra D, Poulet FM, et al. Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J Biol Chem. 2004;279(13):12876-12882.
19. Lewis HD, Perez Revuelta BI, Nadin A, et al. Catalytic site-directed gamma-secretase complex inhibitors do not discriminate pharmacologically between Notch S3 and beta-APP cleavages. Biochemistry. 2003;42(24):7580-7586.
20. Lanz TA, Hosley JD, Adams WJ, Merchant KM. Studies of Abeta pharmacodynamics in the brain, cerebrospinal fluid, and plasma in young (plaque-free) Tg2576 mice using the gamma-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-di hydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY-411575). J Pharmacol Exp Ther. 2004;309(1):49-55.
21. Hyde LA, McHugh NA, Chen J, et al. Studies to investigate the in vivo therapeutic window of the gamma-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-di hydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY411,575) in the CRND8 mouse. J Pharmacol Exp Ther. 2006;319(3):1133-1143.
22. Siemers E, Skinner M, Dean RA, et al. Safety, tolerability, and changes in amyloid beta concentrations after administration of a gamma-secretase inhibitor in volunteers. Clin Neuropharmacol. 2005;28(3):126-132.
23. Henley DB, May PC, Dean RA, Siemers ER. Development of semagacestat (LY450139), a functional gamma-secretase inhibitor, for the treatment of Alzheimer's disease. Expert Opin Pharmacother. 2009;10(10):1657-1664.
24. Luistro L, He W, Smith M, et al. Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties. Cancer Res. 2009;69(19):7672-7680.
25. Han J, Ma I, Hendzel MJ, Allalunis-Turner J. The cytotoxicity of gamma-secretase inhibitor I to breast cancer cells is mediated by proteasome inhibition, not by gamma-secretase inhibition. Breast Cancer Res. 2009;11(4):R57.
26. Weihofen A, Lemberg MK, Friedmann E, et al. Targeting presenilin-type aspartic protease signal peptide peptidase with gamma-secretase inhibitors. J Biol Chem. 2003;278(19):16528-16533.
27. Golde TE, Wolfe MS, Greenbaum DC. Signal peptide peptidases: a family of intramembrane-cleaving proteases that cleave type 2 transmembrane proteins. Semin Cell Dev Biol. 2009;20(2):225-230.
28. Yan D, Qin N, Zhang H, et al. Expression of TNF-alpha leader sequence renders MCF-7 tumor cells resistant to the cytotoxicity of soluble TNF-alpha. Breast Cancer Res Treat. 2009;116(1):91-102.
29. Dong Y, Li A, Wang J, Weber JD, Michel LS. Synthetic lethality through combined Notch-epidermal growth factor receptor pathway inhibition in basal-like breast cancer. Cancer Res. 2010;70(13):5465-5474.
30. Filipovic A, Gronau JH, Green AR, et al. Biological and clinical implications of nicastrin expression in invasive breast cancer. Breast Cancer Res Treat. 2011;125(1):43-53.
31. Kopan R, Ilagan MX. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell. 2009;137(2):216-233.
32. Heitzler P. Biodiversity and noncanonical Notch signaling. Curr Top Dev Biol. 2010;92:457-481.
33. Al-Hussaini H, Subramanyam D, Reedijk M, Sridhar SS. Notch signaling pathway as a therapeutic target in breast cancer. Mol Cancer Ther. 2011;10(1):9-15.
34. Rizzo P, Osipo C, Foreman K, Golde T, Osborne B, Miele L. Rational targeting of Notch signaling in cancer. Oncogene. 2008;27(38): 5124-5131.
35. Shi W, Harris AL. Notch signaling in breast cancer and tumor angiogenesis: cross-talk and therapeutic potentials. J Mammary Gland Biol Neoplasia. 2006;11(1):41-52.
36. Harrison H, Farnie G, Brennan KR, Clarke RB. Breast cancer stem cells: something out of notching? Cancer Res. 2010;70(22):8973-8976.
37. Han J, Hendzel MJ, Allalunis-Turner J. Notch signaling as a therapeutic target for breast cancer treatment? Breast Cancer Res. 2011; 13(3):210.
38. Robinson DR, Kalyana-Sundaram S, Wu YM, et al. Functionally recurrent rearrangements of the MAST kinase and Notch gene families in breast cancer. Nat Med. 2011;17(12):1646-1651.
39. Ridgway J, Zhang G, Wu Y, et al. Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature. 2006;444(7122):1083-1087.
40. Noguera-Troise I, Daly C, Papadopoulos NJ, et al. Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Nature. 2006;444(7122):1032-1037.
41. Sethi N, Dai X, Winter CG, Kang Y. Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells. Cancer Cell. 2011;19(2):192-205.
42. Xing F, Okuda H, Watabe M, et al. Hypoxia-induced Jagged2 promotes breast cancer metastasis and self-renewal of cancer stem-like cells. Oncogene. 2011;30(39):4075-4086.
43. Sundvall M, Iljin K, Kilpinen S, Sara H, Kallioniemi OP, Elenius K. Role of ErbB4 in breast cancer. J Mammary Gland Biol Neoplasia. 2008;13(2):259-268.
44. Chuu CP, Chen RY, Barkinge JL, Ciaccio MF, Jones RB. Systems-level analysis of ErbB4 signaling in breast cancer: a laboratory to clinical perspective. Mol Cancer Res. 2008;6(6):885-891.
45. Sartor CI, Zhou H, Kozlowska E, et al. Her4 mediates ligand-dependent antiproliferative and differentiation responses in human breast cancer cells. Mol Cell Biol. 2001;21(13):4265-4275.
46. Ni CY, Murphy MP, Golde TE, Carpenter G. Gamma-secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase. Science. 2001;294(5549):2179-2181.
47. Vidal GA, Naresh A, Marrero L, Jones FE. Presenilin-dependent gamma-secretase processing regulates multiple ERBB4/HER4 activities. J Biol Chem. 2005;280(20):19777-19783.
48. Feng SM, Sartor CI, Hunter D, et al. The HER4 cytoplasmic domain, but not its C terminus, inhibits mammary cell proliferation. Mol Endocrinol. 2007;21(8):1861-1876.
49. Marambaud P, Shioi J, Serban G, et al. A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions. EMBO J. 2002;21(8): 1948-1956.
50. Berx G, Van Roy F. The E-cadherin/catenin complex: an important gatekeeper in breast cancer tumorigenesis and malignant progression. Breast Cancer Res. 2001;3(5):289-293.
51. Ferber EC, Kajita M, Wadlow A, et al. A role for the cleaved cytoplasmic domain of E-cadherin in the nucleus. J Biol Chem. 2008;283(19):12691-12700.
52. Park CS, Kim OS, Yun SM, Jo SA, Jo I, Koh YH. Presenilin 1/gamma-secretase is associated with cadmium-induced E-cadherin cleavage and COX-2 gene expression in T47D breast cancer cells. Toxicol Sci. 2008;106(2):413-422.
53. Lammich S, Okochi M, Takeda M, et al. Presenilin-dependent intramembrane proteolysis of CD44 leads to the liberation of its intracellular domain and the secretion of an Abeta-like peptide. J Biol Chem. 2002;277(47):44754-44759.
54. Murakami D, Okamoto I, Nagano O, et al. Presenilin-dependent gamma-secretase activity mediates the intramembranous cleavage of CD44. Oncogene. 2003;22(10):1511-1516.
55. Marhaba R, Zoller M. CD44 in cancer progression: adhesion, migration and growth regulation. J Mol Histol. 2004;35(3):211-231.
56. Louderbough JM, Schroeder JA. Understanding the dual nature of CD44 in breast cancer progression. Mol Cancer Res. 2011;9(12):1573-1586.
57. Okamoto I, Kawano Y, Murakami D, et al. Proteolytic release of CD44 intracellular domain and its role in the CD44 signaling pathway. J Cell Biol. 2001;155(5):755-762.
58. Pelletier L, Guillaumot P, Freche B, et al. Gamma-secretase-dependent proteolysis of CD44 promotes neoplastic transformation of rat fibroblastic cells. Cancer Res. 2006;66(7):3681-3687.
59. De Falco V, Tamburrino A, Ventre S, et al. CD44 proteolysis increases CREB phosphorylation and sustains proliferation of thyroid cancer cells. Cancer Res. 2012;72(6):1449-1458.
60. Zhang YW, Wang R, Liu Q, Zhang H, Liao FF, Xu H. Presenilin/gamma-secretase-dependent processing of beta-amyloid precursor protein regulates EGF receptor expression. Proc Natl Acad Sci U S A. 2007;104(25):10613-10618.
61. Liu CX, Ranganathan S, Robinson S, Strickland DK. Gamma-secretase-mediated release of the low density lipoprotein receptor-related protein 1B intracellular domain suppresses anchorage-independent growth of neuroglioma cells. J Biol Chem. 2007;282(10):7504-7511.
62. Kim DY, Ingano LA, Carey BW, Pettingell WH, Kovacs DM. Presenilin/gamma-secretase-mediated cleavage of the voltage-gated sodium channel beta2-subunit regulates cell adhesion and migration. J Biol Chem. 2005;280(24):23251-23261.
63. Yamaguchi N, Oyama T, Ito E, et al. NOTCH3 signaling pathway plays crucial roles in the proliferation of ErbB2-negative human breast cancer cells. Cancer Res. 2008;68(6):1881-1888.
64. Rizzo P, Miao H, D'Souza G, et al. Cross-talk between notch and the estrogen receptor in breast cancer suggests novel therapeutic approaches. Cancer Res. 2008;68(13):5226-5235.
65. Osipo C, Patel P, Rizzo P, et al. ErbB-2 inhibition activates Notch-1 and sensitizes breast cancer cells to a gamma-secretase inhibitor. Oncogene. 2008;27(37):5019-5032.
66. Yong T, Sun A, Henry MD, Meyers S, Davis JN. Down regulation of CSL activity inhibits cell proliferation in prostate and breast cancer cells. J Cell Biochem. 2011;112(9):2340-2351.
67. Jackson AL, Bartz SR, Schelter J, et al. Expression profiling reveals off-target gene regulation by RNAi. Nat Biotechnol. 2003;21(6): 635-637.
68. Scacheri PC, Rozenblatt-Rosen O, Caplen NJ, et al. Short interfering RNAs can induce unexpected and divergent changes in the levels of untargeted proteins in mammalian cells. Proc Natl Acad Sci U S A. 2004;101(7):1892-1897.
69. van Es JH, van Gijn ME, Riccio O, et al. Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature. 2005;435(7044):959-963.
70. Fleisher AS, Raman R, Siemers ER, et al. Phase 2 safety trial targeting amyloid beta production with a gamma-secretase inhibitor in Alzheimer disease. Arch Neurol. 2008;65(8):1031-1038.
71. Tammam J, Ware C, Efferson C, et al. Down-regulation of the Notch pathway mediated by a gamma-secretase inhibitor induces anti-tumour effects in mouse models of T-cell leukaemia. Br J Pharmacol. 2009;158(5):1183-1195.
72. Real PJ, Tosello V, Palomero T, et al. Gamma-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia. Nat Med. 2009;15(1):50-58.
73. Radtke F, Fasnacht N, Macdonald HR. Notch signaling in the immune system. Immunity. 2010;32(1):14-27.
74. Dou GR, Wang YC, Hu XB, et al. RBP-J, the transcription factor downstream of Notch receptors, is essential for the maintenance of vascular homeostasis in adult mice. FASEB J. 2008;22(5):1606-1617.
75. Yan M, Callahan CA, Beyer JC, et al. Chronic DLL4 blockade induces vascular neoplasms. Nature. 2010;463(7282):E6-E7.
76. Liu Z, Turkoz A, Jackson EN, et al. Notch1 loss of heterozygosity causes vascular tumors and lethal hemorrhage in mice. J Clin Invest. 2011;121(2):800-808.
77. Demehri S, Turkoz A, Kopan R. Epidermal Notch1 loss promotes skin tumorigenesis by impacting the stromal microenvironment. Cancer Cell. 2009;16(1):55-66.
78. Nicolas M, Wolfer A, Raj K, et al. Notch1 functions as a tumor suppressor in mouse skin. Nat Genet. 2003;33(3):416-421.
79. Extance A. Alzheimer's failure raises questions about disease-modifying strategies. Nat Rev Drug Discov. 2010;9(10):749-751.
80. Wang NJ, Sanborn Z, Arnett KL, et al. Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma. Proc Natl Acad Sci U S A. 2011;108(43):17761-17766.
81. Kondratyev M, Kreso A, Hallett RM, et al. Gamma-secretase inhibitors target tumor-initiating cells in a mouse model of ERBB2 breast cancer. Oncogene. 2012;31(1):93-103.
82. Efferson CL, Winkelmann CT, Ware C, et al. Downregulation of Notch pathway by a gamma-secretase inhibitor attenuates AKT/mammalian target of rapamycin signaling and glucose uptake in an ERBB2 transgenic breast cancer model. Cancer Res. 2010;70(6):2476-2484.
83. Watters JW, Cheng C, Majumder PK, et al. De novo discovery of a gamma-secretase inhibitor response signature using a novel in vivo breast tumor model. Cancer Res. 2009;69(23):8949-8957.