The phosphorylated prodrug FTY720 is a histone deacetylase inhibitor that reactivates ERα expression and enhances hormonal therapy for breast cancer

Oncogenesis

Volumn 4, Issue 6, 2015, Pages

  Hait, N C ^a   Avni, D ^a   Yamada, A ^b   Nagahashi, M ^b   Aoyagi, T ^b   Aoki, H ^b   Dumur, C I ^c   Zelenko, Z ^d   Gallagher, E J ^d   Leroith, D ^d   Milstien, S ^a   Takabe, K ^b   Spiegel, S ^a  

^a VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

^b VIRGINIA COMMONWEALTH UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

^d MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ESTROGEN RECEPTOR; ESTROGEN RECEPTOR ALPHA; FINGOLIMOD; HISTONE DEACETYLASE 1; PROGESTERONE RECEPTOR; SPHINGOSINE 1 PHOSPHATE RECEPTOR; SPHINGOSINE KINASE 2; TAMOXIFEN; VORINOSTAT;

ADVANCED CANCER; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BREAST CANCER; BREAST CANCER CELL LINE; BREAST CARCINOGENESIS; CANCER GROWTH; CANCER HORMONE THERAPY; CANCER PROGNOSIS; CELL NUCLEUS; CONTROLLED STUDY; ENZYME ACTIVITY; FEMALE; GENE EXPRESSION; GENE EXPRESSION REGULATION; HISTONE ACETYLATION; HUMAN; HUMAN CELL; LIPID DIET; MALE; MICROARRAY ANALYSIS; MOUSE; NONHUMAN; OBESITY; PHOSPHORYLATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; TRIPLE NEGATIVE BREAST CANCER;

EID: 84991010539     PISSN: None     EISSN: 21579024     Source Type: Journal    
DOI: 10.1038/oncsis.2015.16     Document Type: Article

References (58)

1. Clarke R, Leonessa F, Welch JN, Skaar TC. Cellular and molecular pharmacology of antiestrogen action and resistance. Pharmacol Rev 2001; 53: 25-71.
2. McDonnell DP, Norris JD. Connections and regulation of the human estrogen receptor. Science 2002; 296: 1642-1644.
3. Bayraktar S, Gluck S. Molecularly targeted therapies for metastatic triple-negative breast cancer. Breast Cancer Res Treat 2013; 138: 21-35.
4. Phipps AI, Chlebowski RT, Prentice R, McTiernan A, Stefanick ML, Wactawski-Wende J et al. Body size, physical activity, and risk of triple-negative and estrogen receptor-positive breast cancer. Cancer Epidemiol Biomarkers Prev 2011; 20: 454-463.
5. Pierobon M, Frankenfeld CL. Obesity as a risk factor for triple-negative breast cancers: a systematic review and meta-analysis. Breast Cancer Res Treat 2013; 137: 307-314.
6. Zhou Q, Atadja P, Davidson NE. Histone deacetylase inhibitor LBH589 reactivates silenced estrogen receptor alpha (ER) gene expression without loss of DNA hypermethylation. Cancer Biol Ther 2007; 6: 64-69.
7. Keen JC, Yan L, Mack KM, Pettit C, Smith D, Sharma D et al. A novel histone deacetylase inhibitor, scriptaid, enhances expression of functional estrogen receptor alpha (ER) in ER negative human breast cancer cells in combination with 5-aza 2'-deoxycytidine. Breast Cancer Res Treat 2003; 81: 177-186.
8. Restall C, Doherty J, Liu HB, Genovese R, Paiman L, Byron KA et al. A novel histone deacetylase inhibitor augments tamoxifen-mediated attenuation of breast carcinoma growth. Int J Cancer 2009; 125: 483-487.
9. Munster PN, Thurn KT, Thomas S, Raha P, Lacevic M, Miller A et al. A phase II study of the histone deacetylase inhibitor vorinostat combined with tamoxifen for the treatment of patients with hormone therapy-resistant breast cancer. Br J Cancer 2011; 104: 1828-1835.
10. Brinkmann V, Billich A, Baumruker T, Heining P, Schmouder R, Francis G et al. Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov 2010; 9: 883-897.
11. Azuma H, Takahara S, Ichimaru N, Wang JD, Itoh Y, Otsuki Y et al. Marked prevention of tumor growth and metastasis by a novel immunosuppressive agent, FTY720, in mouse breast cancer models. Cancer Res 2002; 62: 1410-1419.
12. Mousseau Y, Mollard S, Faucher-Durand K, Richard L, Nizou A, Cook-Moreau J et al. Fingolimod potentiates the effects of sunitinib malate in a rat breast cancer model. Breast Cancer Res Treat 2012; 134: 31-40.
13. Pitman MR, Woodcock JM, Lopez AF, Pitson SM. Molecular targets of FTY720 (fingolimod). Curr Mol Med 2012; 12: 1207-1219.
14. Lee H, Deng J, Kujawski M, Yang C, Liu Y, Herrmann A et al. STAT3-induced S1PR1 expression is crucial for persistent STAT3 activation in tumors. Nat Med 2010; 16: 1421-1428.
15. Deng J, Liu Y, Lee H, Herrmann A, Zhang W, Zhang C et al. S1PR1-STAT3 signaling is crucial for myeloid cell colonization at future metastatic sites. Cancer Cell 2012; 21: 642-654.
16. Liang J, Nagahashi M, Kim EY, Harikumar KB, Yamada A, Huang WC et al. Sphingosine-1-phosphate links persistent STAT3 activation, chronic intestinal inflammation, and development of colitis-associated cancer. Cancer Cell 2013; 23: 107-120.
17. Saddoughi SA, Gencer S, Peterson YK, Ward KE, Mukhopadhyay A, Oaks J et al. Sphingosine analogue drug FTY720 targets I2PP2A/SET and mediates lung tumour suppression via activation of PP2A-RIPK1-dependent necroptosis. EMBO Mol Med 2013; 5: 105-121.
18. Perrotti D, Neviani P. Protein phosphatase 2A: a target for anticancer therapy. Lancet Oncol 2013; 14: e229-e238.
19. Hait NC, Wise LE, Allegood JC, O'Brien M, Avni D, Reeves TM et al. Active, phosphorylated fingolimod inhibits histone deacetylases and facilitates fear extinction memory. Nat Neurosci 2014; 17: 971-980.
20. Mandala S, Hajdu R, Bergstrom J, Quackenbush E, Xie J, Milligan J et al. Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science 2002; 296: 346-349.
21. Glozak MA, Seto E. Histone deacetylases and cancer. Oncogene 2007; 26: 5420-5432.
22. Barneda-Zahonero B, Parra M. Histone deacetylases and cancer. Mol Oncol 2012; 6: 579-589.
23. Spiegel S, Milstien S, Grant S. Endogenous modulators and pharmacological inhibitors of histone deacetylases in cancer therapy. Oncogene 2012; 31: 537-551.
24. Delcuve GP, Khan DH, Davie JR. Targeting class I histone deacetylases in cancer therapy. Expert Opin Ther Targets 2013; 17: 29-41.
25. Sieri S, Chiodini P, Agnoli C, Pala V, Berrino F, Trichopoulou A et al. Dietary fat intake and development of specific breast cancer subtypes. J Natl Cancer Inst 2014; 106: dju068 doi: 10.1093/jnci/dju068.
26. Maglione JE, Moghanaki D, Young LJ, Manner CK, Ellies LG, Joseph SO et al. Transgenic polyoma middle-T mice model premalignant mammary disease. Cancer Res 2001; 61: 8298-8305.
27. Lin EY, Jones JG, Li P, Zhu L, Whitney KD, Muller WJ et al. Progression to malignancy in the polyoma middle T oncoprotein mouse breast cancer model provides a reliable model for human diseases. Am J Pathol 2003; 163: 2113-2126.
28. La Merrill M, Gordon RR, Hunter KW, Threadgill DW, Pomp D. Dietary fat alters pulmonary metastasis of mammary cancers through cancer autonomous and non-autonomous changes in gene expression. Clin Exp Metastasis 2010; 27: 107-116.
29. Llaverias G, Danilo C, Mercier I, Daumer K, Capozza F, Williams TM et al. Role of cholesterol in the development and progression of breast cancer. Am J Pathol 2011; 178: 402-412.
30. Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med 2010; 363: 1938-1948.
31. Jang ER, Lim SJ, Lee ES, Jeong G, Kim TY, Bang YJ et al. The histone deacetylase inhibitor trichostatin A sensitizes estrogen receptor alpha-negative breast cancer cells to tamoxifen. Oncogene 2004; 23: 1724-1736.
32. Huang Y, Vasilatos SN, Boric L, Shaw PG, Davidson NE. Inhibitors of histone demethylation and histone deacetylation cooperate in regulating gene expression and inhibiting growth in human breast cancer cells. Breast Cancer Res Treat 2012; 131: 777-789.
33. Tate CR, Rhodes LV, Segar HC, Driver JL, Pounder FN, Burow ME et al. Targeting triple-negative breast cancer cells with the histone deacetylase inhibitor panobinostat. Breast Cancer Res 2012; 14: R79.
34. Li Y, Meeran SM, Patel SN, Chen H, Hardy TM, Tollefsbol TO. Epigenetic reactivation of estrogen receptor-alpha (ERalpha) by genistein enhances hormonal therapy sensitivity in ERalpha-negative breast cancer. Mol Cancer 2013; 12: 9.
35. Nagahashi M, Ramachandran S, Kim EY, Allegood JC, Rashid OM, Yamada A et al. Sphingosine-1-phosphate produced by sphingosine kinase 1 promotes breast cancer progression by stimulating angiogenesis and lymphangiogenesis. Cancer Res 2012; 72: 726-735.
36. Rashid OM, Nagahashi M, Ramachandran S, Dumur C, Schaum J, Yamada A et al. An improved syngeneic orthotopic murine model of human breast cancer progression. Breast Cancer Res Treat 2014; 147: 501-512.
37. Muller BM, Jana L, Kasajima A, Lehmann A, Prinzler J, Budczies J et al. Differential expression of histone deacetylases HDAC1, 2 and 3 in human breast cancer - overexpression of HDAC2 and HDAC3 is associated with clinicopathological indicators of disease progression. BMC Cancer 2013; 13: 215.
38. Aagaard-Tillery KM, Grove K, Bishop J, Bishop J, Ke X, Fu Q et al. Developmental origins of disease and determinants of chromatin structure: maternal diet modifies the primate fetal epigenome. J Mol Endocrinol 2008; 41: 91-102.
39. Tang FY, Pai MH, Chiang EP. Consumption of high-fat diet induces tumor progression and epithelial-mesenchymal transition of colorectal cancer in a mouse xenograft model. J Nutr Biochem 2012; 23: 1302-1313.
40. Sabnis GJ, Goloubeva O, Chumsri S, Nguyen N, Sukumar S, Brodie AM. Functional activation of the estrogen receptor-alpha and aromatase by the HDAC inhibitor entinostat sensitizes ER-negative tumors to letrozole. Cancer Res 2011; 71: 1893-1903.
41. Yardley DA, Ismail-Khan RR, Melichar B, Lichinitser M, Munster PN, Klein PM et al. Randomized phase II, double-blind, placebo-controlled study of exemestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on treatment with a nonsteroidal aromatase inhibitor. J Clin Oncol 2013; 31: 2128-2135.
42. Don AS, Martinez-Lamenca C, Webb WR, Proia RL, Roberts E, Rosen H. Essential requirement for sphingosine kinase 2 in a sphingolipid apoptosis pathway activated by FTY720 analogs. J Biol Chem 2007; 282: 15833-15842.
43. Zhang L, Wang HD, Ji XJ, Cong ZX, Zhu JH, Zhou Y. FTY720 for cancer therapy (Review). Oncol Rep 2013; 30: 2571-2578.
44. Baldacchino S, Saliba C, Petroni V, Fenech AG, Borg N, Grech G. Deregulation of the phosphatase, PP2A is a common event in breast cancer, predicting sensitivity to FTY720. EPMA J 2014; 5: 3.
45. Lim KG, Tonelli F, Li Z, Lu X, Bittman R, Pyne S et al. FTY720 analogues as sphingosine kinase 1 inhibitors: enzyme inhibition kinetics, allosterism, proteasomal degradation, and actin rearrangment in MCF-7 breast cancer cells. J Biol Chem 2011; 286: 18633-18640.
46. Ruckhaberle E, Rody A, Engels K, Gaetje R, von Minckwitz G, Schiffmann S et al. Microarray analysis of altered sphingolipid metabolism reveals prognostic significance of sphingosine kinase 1 in breast cancer. Breast Cancer Res Treat 2008; 112: 41-52.
47. Pyne NJ, Pyne S. Sphingosine 1-phosphate and cancer. Nat Rev Cancer 2010; 10: 489-503.
48. Kunkel GT, Maceyka M, Milstien S, Spiegel S. Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond. Nat Rev Drug Discov 2013; 12: 688-702.
49. Datta A, Loo SY, Huang B, Wong L, Tan SS, Tan TZ et al. SPHK1 regulates proliferation and survival responses in triple-negative breast cancer. Oncotarget 2014; 5: 5920-5933.
50. Watson C, Long JS, Orange C, Tannahill CL, Mallon E, McGlynn LM et al. High expression of sphingosine 1-phosphate receptors, S1P1 and S1P3, sphingosine kinase 1, and extracellular signal-regulated kinase-1/2 is associated with development of tamoxifen resistance in estrogen receptor-positive breast cancer patients. Am J Pathol 2010; 177: 2205-2215.
51. Rutherford C, Childs S, Ohotski J, McGlynn L, Riddick M, Mac F et al. Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of Bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1. Cell Death Dis 2013; 4: e927.
52. Priceman SJ, Shen S, Wang L, Deng J, Yue C, Kujawski M et al. S1PR1 is crucial for accumulation of regulatory T cells in tumors via STAT3. Cell Rep 2014; 6: 992-999.
53. Spranger S, Koblish HK, Horton B, Scherle PA, Newton R, Gajewski TF. Mechanism of tumor rejection with doublets of CTLA-4, PD-1/PD-L1, or IDO blockade involves restored IL-2 production and proliferation of CD8(+) T cells directly within the tumor microenvironment. J Immunother Cancer 2014; 2: 3.
54. Hait NC, Allegood J, Maceyka M, Strub GM, Harikumar KB, Singh SK et al. Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate. Science 2009; 325: 1254-1257.
55. Sarkar S, Maceyka M, Hait NC, Paugh SW, Sankala H, Milstien S et al. Sphingosine kinase 1 is required for migration, proliferation and survival of MCF-7 human breast cancer cells. FEBS Lett 2005; 579: 5313-5317.
56. Dumur CI, Nasim S, Best AM, Archer KJ, Ladd AC, Mas VR et al. Evaluation of quality-control criteria for microarray gene expression analysis. Clin Chem 2004; 50: 1994-2002.
57. Irizarry RA, Bolstad BM, Collin F, Cope LM, Hobbs B, Speed TP. Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res 2003; 31: e15.
58. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 2004; 5: R80.