Epigenetic modulators mitigate angiogenesis through a complex transcriptomic network

[en] In this review, we summarize the knowledge pertaining to the role of epigenetics in the regulation of angiogenesis. In particular, we show that lysine acetylation and cytosine methylation are important transcriptional regulators of angiogenic genes in endothelial cells. Lysine acetylation and cytosine methylation inhibitors idiosyncratically tune the transcriptome and affect expression of key modulators of angiogenesis such as VEGF and eNOS. Transcriptomic profiling also reveals a series of novel genes that are concomitantly affected by epigenetic modulators. The reversibility and overall tolerability of currently available epigenetic inhibitors open up the prospect of therapeutic intervention in pathologies where angiogenesis is exacerbated. This type of multitargeted strategy has the major advantage of overcoming the compensatory feedback mechanisms that characterize single anti-angiogenic factors.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Shiva Shankar, T.V.

Willems, Luc ; Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.

Language :

English

Title :

Epigenetic modulators mitigate angiogenesis through a complex transcriptomic network

Publication date :

February 2014

Journal title :

Vascular Pharmacology

ISSN :

1537-1891

Publisher :

Elsevier Science, New York, United States - New York

Volume :

Pages :

57-66

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 27 February 2014

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Bibliography

Carmeliet P. Angiogenesis in life, disease and medicine. Nature 2005, 438(7070):932-936. 10.1038/nature04478.
Carmeliet P. Angiogenesis in health and disease. Nat Med 2003, 9(6):653-660. 10.1038/nm0603-653.
Ferrara N., Kerbel R.S. Angiogenesis as a therapeutic target. Nature 2005, 438(7070):967-974. 10.1038/nature04483.
Kalra M., Rao N., Nanda K., Rehman F., Girish K.L., Tippu S., et al. The role of mast cells on angiogenesis in oral squamous cell carcinoma. Med Oral Patol Oral Cir Bucal 2012, 17(2):e190-e196.
Boehm T., Folkman J., Browder T., O'Reilly M.S. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 1997, 390(6658):404-407. 10.1038/37126.
Bergers G., Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 2008, 8(8):592-603. 10.1038/nrc2442.
Carmeliet P., De Smet F., Loges S., Mazzone M. Branching morphogenesis anda antiangiogenesis candidates: tip cells lead the way. Nat Rev Clin Oncol 2009, 6(6):315-326. 10.1038/nrclinonc.2009.64.
Golbabapour S., Abdulla M.A., Hajrezaei M. A concise review on epigenetic regulation: insight into molecular mechanisms. Int J Mol Sci 2011, 12(12):8661-8694. 10.3390/ijms12128661.
Jamal A., Man H.S., Marsden P.A. Gene regulation in the vascular endothelium: why epigenetics is important for the kidney. Semin Nephrol 2012, 32(2):176-184. 10.1016/j.semnephrol.2012.02.009.
Hellebrekers D.M., Griffioen A.W., van Engeland M. Dual targeting of epigenetic therapy in cancer. Biochim Biophys Acta 2007, 1775(1):76-91. 10.1016/j.bbcan.2006.07.003.
Felsenfeld G., Groudine M. Controlling the double helix. Nature 2003, 421(6921):448-453. 10.1038/nature01411.
Cheng H.T., Hung W.C. Inhibition of proliferation, sprouting, tube formation and Tie2 signaling of lymphatic endothelial cells by the histone deacetylase inhibitor SAHA. Oncol Rep 2013, 30(2):961-967. 10.3892/or.2013.2523.
Byler T.K., Leocadio D., Shapiro O., Bratslavsky G., Stodgell C.J., Wood R.W., et al. Valproic acid decreases urothelial cancer cell proliferation and induces thrombospondin-1 expression. BMC Urol 2012, 12:21. 10.1186/1471-2490-12-21.
Yang Q.W., Liu S., Tian Y., Salwen H.R., Chlenski A., Weinstein J., et al. Methylation-associated silencing of the thrombospondin-1 gene in human neuroblastoma. Cancer Res 2003, 63(19):6299-6310.
Li Q., Ahuja N., Burger P.C., Issa J.P. Methylation and silencing of the thrombospondin-1 promoter in human cancer. Oncogene 1999, 18(21):3284-3289. 10.1038/sj.onc.1202663.
Alleman W.G., Tabios R.L., Chandramouli G.V., Aprelikova O.N., Torres-Cabala C., Mendoza A., et al. The in vitro and in vivo effects of re-expressing methylated von Hippel-Lindau tumor suppressor gene in clear cell renal carcinoma with 5-aza-2'-deoxycytidine. Clin Cancer Res 2004, 10(20):7011-7021. 10.1158/1078-0432.CCR-04-0516.
Cheng J.C., Matsen C.B., Gonzales F.A., Ye W., Greer S., Marquez V.E., et al. Inhibition of DNA methylation and reactivation of silenced genes by zebularine. J Natl Cancer Inst 2003, 95(5):399-409.
Qian D.Z., Wang X., Kachhap S.K., Kato Y., Wei Y., Zhang L., et al. The histone deacetylase inhibitor NVP-LAQ824 inhibits angiogenesis and has a greater antitumor effect in combination with the vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584. Cancer Res 2004, 64(18):6626-6634. 10.1158/0008-5472.CAN-04-0540.
Sawa H., Murakami H., Ohshima Y., Murakami M., Yamazaki I., Tamura Y., et al. Histone deacetylase inhibitors such as sodium butyrate and trichostatin A inhibit vascular endothelial growth factor (VEGF) secretion from human glioblastoma cells. Brain Tumor Pathol 2002, 19(2):77-81.
Kouzarides T. Chromatin modifications and their function. Cell 2007, 128(4):693-705. 10.1016/j.cell.2007.02.005.
Dokmanovic M., Clarke C., Marks P.A. Histone deacetylase inhibitors: overview and perspectives. Mol Cancer Res 2007, 5(10):981-989. 10.1158/1541-7786.MCR-07-0324.
Johnstone R.W., Licht J.D. Histone deacetylase inhibitors in cancer therapy: is transcription the primary target?. Cancer Cell 2003, 4(1):13-18.
Marks P.A., Richon V.M., Miller T., Kelly W.K. Histone deacetylase inhibitors. Adv Cancer Res 2004, 91:137-168. 10.1016/S0065-230X(04)91004-4.
Eberharter A., Becker P.B. Histone acetylation: a switch between repressive and permissive chromatin. Second in review series on chromatin dynamics. EMBO Rep 2002, 3(3):224-229. 10.1093/embo-reports/kvf053.
Gregory P.D., Wagner K., Horz W. Histone acetylation and chromatin remodeling. Exp Cell Res 2001, 265(2):195-202. 10.1006/excr.2001.5187.
Saha R.N., Pahan K. HATs and HDACs in neurodegeneration: a tale of disconcerted acetylation homeostasis. Cell Death Differ 2006, 13(4):539-550. 10.1038/sj.cdd.4401769.
Villar-Garea A., Esteller M. Histone deacetylase inhibitors: understanding a new wave of anticancer agents. Int J Cancer 2004, 112(2):171-178. 10.1002/ijc.20372.
Roth S.Y., Denu J.M., Allis C.D. Histone acetyltransferases. Annu Rev Biochem 2001, 70:81-120. 10.1146/annurev.biochem.70.1.81.
Thiagalingam S., Cheng K.H., Lee H.J., Mineva N., Thiagalingam A., Ponte J.F. Histone deacetylases: unique players in shaping the epigenetic histone code. Ann N Y Acad Sci 2003, 983:84-100.
Yang X.J., Seto E. HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention. Oncogene 2007, 26(37):5310-5318. 10.1038/sj.onc.1210599.
Kim M.S., Kwon H.J., Lee Y.M., Baek J.H., Jang J.E., Lee S.W., et al. Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes. Nat Med 2001, 7(4):437-443. 10.1038/86507.
Zampetaki A., Zeng L., Margariti A., Xiao Q., Li H., Zhang Z., et al. Histone deacetylase 3 is critical in endothelial survival and atherosclerosis development in response to disturbed flow. Circulation 2010, 121(1):132-142. 10.1161/CIRCULATIONAHA.109.890491.
Urbich C., Rossig L., Kaluza D., Potente M., Boeckel J.N., Knau A., et al. HDAC5 is a repressor of angiogenesis and determines the angiogenic gene expression pattern of endothelial cells. Blood 2009, 113(22):5669-5679. 10.1182/blood-2009-01-196485.
Kaluza D., Kroll J., Gesierich S., Yao T.P., Boon R.A., Hergenreider E., et al. Class IIb HDAC6 regulates endothelial cell migration and angiogenesis by deacetylation of cortactin. EMBO J 2011, 30(20):4142-4156. 10.1038/emboj.2011.298.
Chang S., Young B.D., Li S., Qi X., Richardson J.A., Olson E.N. Histone deacetylase 7 maintains vascular integrity by repressing matrix metalloproteinase 10. Cell 2006, 126(2):321-334. 10.1016/j.cell.2006.05.040.
Mottet D., Bellahcene A., Pirotte S., Waltregny D., Deroanne C., Lamour V., et al. Histone deacetylase 7 silencing alters endothelial cell migration, a key step in angiogenesis. Circ Res 2007, 101(12):1237-1246. 10.1161/CIRCRESAHA.107.149377.
Kaluza D., Kroll J., Gesierich S., Manavski Y., Boeckel J.N., Doebele C., et al. Histone deacetylase 9 promotes angiogenesis by targeting the antiangiogenic microRNA-17-92 cluster in endothelial cells. Arterioscler Thromb Vasc Biol 2013, 33(3):533-543. 10.1161/ATVBAHA.112.300415.
Lappas M. Anti-inflammatory properties of sirtuin 6 in human umbilical vein endothelial cells. Mediators Inflamm 2012, 2012:11. 10.1155/2012/597514.
Johnstone R.W. Histone-deacetylase inhibitors: novel drugs for the treatment of cancer. Nat Rev Drug Discov 2002, 1(4):287-299. 10.1038/nrd772.
Kim T.Y., Bang Y.J., Robertson K.D. Histone deacetylase inhibitors for cancer therapy. Epigenetics 2006, 1(1):14-23.
Glaser K.B., Staver M.J., Waring J.F., Stender J., Ulrich R.G., Davidsen S.K. Gene expression profiling of multiple histone deacetylase (HDAC) inhibitors: defining a common gene set produced by HDAC inhibition in T24 and MDA carcinoma cell lines. Mol Cancer Ther 2003, 2(2):151-163.
Liu T., Kuljaca S., Tee A., Marshall G.M. Histone deacetylase inhibitors: multifunctional anticancer agents. Cancer Treat Rev 2006, 32(3):157-165. 10.1016/j.ctrv.2005.12.006.
Mitsiades C.S., Mitsiades N.S., McMullan C.J., Poulaki V., Shringarpure R., Hideshima T., et al. Transcriptional signature of histone deacetylase inhibition in multiple myeloma: biological and clinical implications. Proc Natl Acad Sci U S A 2004, 101(2):540-545. 10.1073/pnas.2536759100.
Peart M.J., Smyth G.K., van Laar R.K., Bowtell D.D., Richon V.M., Marks P.A., et al. Identification and functional significance of genes regulated by structurally different histone deacetylase inhibitors. Proc Natl Acad Sci U S A 2005, 102(10):3697-3702. 10.1073/pnas.0500369102.
Acharya M.R., Sparreboom A., Venitz J., Figg W.D. Rational development of histone deacetylase inhibitors as anticancer agents: a review. Mol Pharmacol 2005, 68(4):917-932. 10.1124/mol.105.014167.
Bhalla K.N. Epigenetic and chromatin modifiers as targeted therapy of hematologic malignancies. J Clin Oncol 2005, 23(17):3971-3993. 10.1200/JCO.2005.16.600.
Drummond D.C., Noble C.O., Kirpotin D.B., Guo Z., Scott G.K., Benz C.C. Clinical development of histone deacetylase inhibitors as anticancer agents. Annu Rev Pharmacol Toxicol 2005, 45:495-528. 10.1146/annurev.pharmtox.45.120403.095825.
Kim H.J., Bae S.C. Histone deacetylase inhibitors: molecular mechanisms of action and clinical trials as anti-cancer drugs. Am. J Transl Res 2011, 3(2):166-179.
Monneret C. Histone deacetylase inhibitors. Eur J Med Chem 2005, 40(1):1-13. 10.1016/j.ejmech.2004.10.001.
Greshock T.J., Johns D.M., Noguchi Y., Williams R.M. Improved total synthesis of the potent HDAC inhibitor FK228 (FR-901228). Org Lett 2008, 10(4):613-616. 10.1021/ol702957z.
Michaelis M., Michaelis U.R., Fleming I., Suhan T., Cinatl J., Blaheta R.A., et al. Valproic acid inhibits angiogenesis in vitro and in vivo. Mol Pharmacol 2004, 65(3):520-527. 10.1124/mol.65.3.520.
Hellebrekers D.M., Jair K.W., Vire E., Eguchi S., Hoebers N.T., Fraga M.F., et al. Angiostatic activity of DNA methyltransferase inhibitors. Mol Cancer Ther 2006, 5(2):467-475. 10.1158/1535-7163.MCT-05-0417.
Buysschaert I., Schmidt T., Roncal C., Carmeliet P., Lambrechts D. Genetics, epigenetics and pharmaco-(epi)genomics in angiogenesis. J Cell Mol Med 2008, 12(6B):2533-2551. 10.1111/j.1582-4934.2008.00515.x.
Mahon P.C., Hirota K., Semenza G.L. FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev 2001, 15(20):2675-2686. 10.1101/gad.924501.
Sahin M., Sahin E., Gumuslu S., Erdogan A., Gultekin M. DNA methylation or histone modification status in metastasis and angiogenesis-related genes: a new hypothesis on usage of DNMT inhibitors and S-adenosylmethionine for genome stability. Cancer Metastasis Rev 2010, 29(4):655-676. 10.1007/s10555-010-9253-0.
Deroanne C.F., Bonjean K., Servotte S., Devy L., Colige A., Clausse N., et al. Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling. Oncogene 2002, 21(3):427-436. 10.1038/sj.onc.1205108.
Miao H.Q., Soker S., Feiner L., Alonso J.L., Raper J.A., Klagsbrun M. Neuropilin-1 mediates collapsin-1/semaphorin III inhibition of endothelial cell motility: functional competition of collapsin-1 and vascular endothelial growth factor-165. J Cell Biol 1999, 146(1):233-242.
Ravi R., Mookerjee B., Bhujwalla Z.M., Sutter C.H., Artemov D., Zeng Q., et al. Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev 2000, 14(1):34-44.
Stratmann R., Krieg M., Haas R., Plate K.H. Putative control of angiogenesis in hemangioblastomas by the von Hippel-Lindau tumor suppressor gene. J Neuropathol Exp Neurol 1997, 56(11):1242-1252.
Royds J.A., Dower S.K., Qwarnstrom E.E., Lewis C.E. Response of tumour cells to hypoxia: role of p53 and NFkB. Mol Pathol 1998, 51(2):55-61.
Rossig L., Li H., Fisslthaler B., Urbich C., Fleming I., Forstermann U., et al. Inhibitors of histone deacetylation downregulate the expression of endothelial nitric oxide synthase and compromise endothelial cell function in vasorelaxation and angiogenesis. Circ Res 2002, 91(9):837-844.
Ignarro L.J., Buga G.M., Wood K.S., Byrns R.E., Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A 1987, 84(24):9265-9269.
Duplain H., Burcelin R., Sartori C., Cook S., Egli M., Lepori M., et al. Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase. Circulation 2001, 104(3):342-345.
Fish J.E., Matouk C.C., Rachlis A., Lin S., Tai S.C., D'Abreo C., et al. The expression of endothelial nitric-oxide synthase is controlled by a cell-specific histone code. J Biol Chem 2005, 280(26):24824-24838. 10.1074/jbc.M502115200.
Ohtani K., Vlachojannis G.J., Koyanagi M., Boeckel J.N., Urbich C., Farcas R., et al. Epigenetic regulation of endothelial lineage committed genes in pro-angiogenic hematopoietic and endothelial progenitor cells. Circ Res 2011, 109(11):1219-1229. 10.1161/CIRCRESAHA.111.247304.
Siuda D., Zechner U., El Hajj N., Prawitt D., Langer D., Xia N., et al. Transcriptional regulation of Nox4 by histone deacetylases in human endothelial cells. Basic Res Cardiol 2012, 107(5):283. 10.1007/s00395-012-0283-3.
Craige S.M., Chen K., Pei Y., Li C., Huang X., Chen C., et al. NADPH oxidase 4 promotes endothelial angiogenesis through endothelial nitric oxide synthase activation. Circulation 2011, 124(6):731-740. 10.1161/CIRCULATIONAHA.111.030775.
Hellebrekers D.M., Castermans K., Vire E., Dings R.P., Hoebers N.T., Mayo K.H., et al. Epigenetic regulation of tumor endothelial cell anergy: silencing of intercellular adhesion molecule-1 by histone modifications. Cancer Res 2006, 66(22):10770-10777. 10.1158/0008-5472.CAN-06-1609.
Inoue K., Kobayashi M., Yano K., Miura M., Izumi A., Mataki C., et al. Histone deacetylase inhibitor reduces monocyte adhesion to endothelium through the suppression of vascular cell adhesion molecule-1 expression. Arterioscler Thromb Vasc Biol 2006, 26(12):2652-2659. 10.1161/01.ATV.0000247247.89787.e7.
Wang J., Mahmud S.A., Bitterman P.B., Huo Y., Slungaard A. Histone deacetylase inhibitors suppress TF-kappaB-dependent agonist-driven tissue factor expression in endothelial cells and monocytes. J Biol Chem 2007, 282(39):28408-28418. 10.1074/jbc.M703586200.
Belting M., Dorrell M.I., Sandgren S., Aguilar E., Ahamed J., Dorfleutner A., et al. Regulation of angiogenesis by tissue factor cytoplasmic domain signaling. Nat Med 2004, 10(5):502-509. 10.1038/nm1037.
Lawler J. Thrombospondin-1 as an endogenous inhibitor of angiogenesis and tumor growth. J Cell Mol Med 2002, 6(1):1-12.
Hellebrekers D.M., Melotte V., Vire E., Langenkamp E., Molema G., Fuks F., et al. Identification of epigenetically silenced genes in tumor endothelial cells. Cancer Res 2007, 67(9):4138-4148. 10.1158/0008-5472.CAN-06-3032.
Ma C., D'Mello S.R. Neuroprotection by histone deacetylase-7 (HDAC7) occurs by inhibition of c-jun expression through a deacetylase-independent mechanism. J Biol Chem 2011, 286(6):4819-4828. 10.1074/jbc.M110.146860.
Li Q., Shi L., Gui B., Yu W., Wang J., Zhang D., et al. Binding of the JmjC demethylase JARID1B to LSD1/NuRD suppresses angiogenesis and metastasis in breast cancer cells by repressing chemokine CCL14. Cancer Res 2011, 71(21):6899-6908. 10.1158/0008-5472.CAN-11-1523.
Wang P., Zhen H., Zhang J., Zhang W., Zhang R., Cheng X., et al. Survivin promotes glioma angiogenesis through vascular endothelial growth factor and basic fibroblast growth factor in vitro and in vivo. Mol Carcinog 2012, 51(7):586-595. 10.1002/mc.20829.
Presta M., Camozzi M., Salvatori G., Rusnati M. Role of the soluble pattern recognition receptor PTX3 in vascular biology. J Cell Mol Med 2007, 11(4):723-738. 10.1111/j.1582-4934.2007.00061.x.
Park J.E., Lee D.H., Lee J.A., Park S.G., Kim N.S., Park B.C., et al. Annexin A3 is a potential angiogenic mediator. Biochem Biophys Res Commun 2005, 337(4):1283-1287. 10.1016/j.bbrc.2005.10.004.
Morgan E., Kannan-Thulasiraman P., Noy N. Involvement of fatty acid binding protein 5 and PPARbeta/delta in prostate cancer cell growth. PPAR Res 2010, 2010. 10.1155/2010/234629.
Jin G., Bausch D., Knightly T., Liu Z., Li Y., Liu B., et al. Histone deacetylase inhibitors enhance endothelial cell sprouting angiogenesis in vitro. Surgery 2011, 150(3):429-435. 10.1016/j.surg.2011.07.001.
Ng M.K., Wu J., Chang E., Wang B.Y., Katzenberg-Clark R., Ishii-Watabe A., et al. A central role for nicotinic cholinergic regulation of growth factor-induced endothelial cell migration. Arterioscler Thromb Vasc Biol 2007, 27(1):106-112. 10.1161/01.ATV.0000251517.98396.4a.
Xu K., Chong D.C., Rankin S.A., Zorn A.M., Cleaver O. Rasip1 is required for endothelial cell motility, angiogenesis and vessel formation. Dev Biol 2009, 329(2):269-279. 10.1016/j.ydbio.2009.02.033.
Tahir S.A., Park S., Thompson T.C. Caveolin-1 regulates VEGF-stimulated angiogenic activities in prostate cancer and endothelial cells. Cancer Biol Ther 2009, 8(23):2286-2296.
Pan Y.M., Yao Y.Z., Zhu Z.H., Sun X.T., Qiu Y.D., Ding Y.T. Caveolin-1 is important for nitric oxide-mediated angiogenesis in fibrin gels with human umbilical vein endothelial cells. Acta Pharmacol Sin 2006, 27(12):1567-1574. 10.1111/j.1745-7254.2006.00462.x.
Nam J.O., Kim J.E., Jeong H.W., Lee S.J., Lee B.H., Choi J.Y., et al. Identification of the alphavbeta3 integrin-interacting motif of betaig-h3 and its anti-angiogenic effect. J Biol Chem 2003, 278(28):25902-25909. 10.1074/jbc.M300358200.
Ivanciu L., Gerard R.D., Tang H., Lupu F., Lupu C. Adenovirus-mediated expression of tissue factor pathway inhibitor-2 inhibits endothelial cell migration and angiogenesis. Arterioscler Thromb Vasc Biol 2007, 27(2):310-316. 10.1161/01.ATV.0000254147.89321.cf.
Olindo S., Belrose G., Gillet N., Rodriguez S., Boxus M., Verlaeten O., et al. Safety of long-term treatment of HAM/TSP patients with valproic acid. Blood 2011, 118(24):6306-6309. 10.1182/blood-2011-04-349910.
Larsson P., Ulfhammer E., Magnusson M., Bergh N., Lunke S., El-Osta A., et al. Role of histone acetylation in the stimulatory effect of valproic acid on vascular endothelial tissue-type plasminogen activator expression. PLoS One 2012, 7(2):e31573. 10.1371/journal.pone.0031573.
Egami K., Murohara T., Aoki M., Matsuishi T. Ischemia-induced angiogenesis: role of inflammatory response mediated by P-selectin. J Leukoc Biol 2006, 79(5):971-976. 10.1189/jlb.0805448.
Garmy-Susini B., Jin H., Zhu Y., Sung R.J., Hwang R., Varner J. Integrin alpha4beta1-VCAM-1-mediated adhesion between endothelial and mural cells is required for blood vessel maturation. J Clin Invest 2005, 115(6):1542-1551. 10.1172/JCI23445.
Felcht M., Luck R., Schering A., Seidel P., Srivastava K., Hu J., et al. Angiopoietin-2 differentially regulates angiogenesis through TIE2 and integrin signaling. J Clin Invest 2012, 122(6):1991-2005. 10.1172/JCI58832.
Kwon H.J., Kim M.S., Kim M.J., Nakajima H., Kim K.W. Histone deacetylase inhibitor FK228 inhibits tumor angiogenesis. Int J Cancer 2002, 97(3):290-296.
Shalaby F., Rossant J., Yamaguchi T.P., Gertsenstein M., Wu X.F., Breitman M.L., et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 1995, 376(6535):62-66. 10.1038/376062a0.
Su G.H., Sohn T.A., Ryu B., Kern S.E. A novel histone deacetylase inhibitor identified by high-throughput transcriptional screening of a compound library. Cancer Res 2000, 60(12):3137-3142.
Halazonetis T.D., Georgopoulos K., Greenberg M.E., Leder P. c-Jun dimerizes with itself and with c-Fos, forming complexes of different DNA binding affinities. Cell 1988, 55(5):917-924.
Xie M., Liu M., He C.S. SIRT1 regulates endothelial Notch signaling in lung cancer. PLoS One 2012, 7(9):e45331. 10.1371/journal.pone.0045331.
Kangaspeska S., Stride B., Metivier R., Polycarpou-Schwarz M., Ibberson D., Carmouche R.P., et al. Transient cyclical methylation of promoter DNA. Nature 2008, 452(7183):112-115. 10.1038/nature06640.
Metivier R., Gallais R., Tiffoche C., Le Peron C., Jurkowska R.Z., Carmouche R.P., et al. Cyclical DNA methylation of a transcriptionally active promoter. Nature 2008, 452(7183):45-50. 10.1038/nature06544.
Watt F., Molloy P.L. Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter. Genes Dev 1988, 2(9):1136-1143.
Nan X., Ng H.H., Johnson C.A., Laherty C.D., Turner B.M., Eisenman R.N., et al. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 1998, 393(6683):386-389. 10.1038/30764.
Hendrich B., Bird A. Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol 1998, 18(11):6538-6547.
Boyes J., Bird A. DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein. Cell 1991, 64(6):1123-1134.
Bestor T.H. Activation of mammalian DNA methyltransferase by cleavage of a Zn binding regulatory domain. EMBO J 1992, 11(7):2611-2617.
Robertson K.D., Ait-Si-Ali S., Yokochi T., Wade P.A., Jones P.L., Wolffe A.P. DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters. Nat Genet 2000, 25(3):338-342. 10.1038/77124.
Rountree M.R., Bachman K.E., Baylin S.B. DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. Nat Genet 2000, 25(3):269-277. 10.1038/77023.
Gray S.G., Ekstrom T.J. The human histone deacetylase family. Exp Cell Res 2001, 262(2):75-83. 10.1006/excr.2000.5080.
Tamaru H., Selker E.U. A histone H3 methyltransferase controls DNA methylation in Neurospora crassa. Nature 2001, 414(6861):277-283. 10.1038/35104508.
Beisel C., Paro R. Silencing chromatin: comparing modes and mechanisms. Nat Rev Genet 2011, 12(2):123-135. 10.1038/nrg2932.
Chen W.Y., Townes T.M. Molecular mechanism for silencing virally transduced genes involves histone deacetylation and chromatin condensation. Proc Natl Acad Sci U S A 2000, 97(1):377-382.
Bachman K.E., Park B.H., Rhee I., Rajagopalan H., Herman J.G., Baylin S.B., et al. Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene. Cancer Cell 2003, 3(1):89-95.
Selker E.U. Trichostatin A causes selective loss of DNA methylation in Neurospora. Proc Natl Acad Sci U S A 1998, 95(16):9430-9435.
Lambert M.-P., Herceg Z. Mechanisms of epigenetic gene silencing. Epigenetic aspects of chronic diseases 2011, 41-53. Springer, London. 10.1007/978-1-84882-644-1_3. H.I. Roach, F. Bronner, R.O.C. Oreffo (Eds.).
Vaissiere T., Sawan C., Herceg Z. Epigenetic interplay between histone modifications and DNA methylation in gene silencing. Mutat Res 2008, 659(1-2):40-48. 10.1016/j.mrrev.2008.02.004.
Cooper M.P., Keaney J.F. Epigenetic control of angiogenesis via DNA methylation. Circulation 2011, 123(25):2916-2918. 10.1161/CIRCULATIONAHA.111.033092.
Rao X., Zhong J., Zhang S., Zhang Y., Yu Q., Yang P., et al. Loss of methyl-CpG-binding domain protein 2 enhances endothelial angiogenesis and protects mice against hind-limb ischemic injury. Circulation 2011, 123(25):2964-2974. 10.1161/CIRCULATIONAHA.110.966408.
Chan Y., Fish J.E., D'Abreo C., Lin S., Robb G.B., Teichert A.M., et al. The cell-specific expression of endothelial nitric-oxide synthase: a role for DNA methylation. J Biol Chem 2004, 279(33):35087-35100. 10.1074/jbc.M405063200.
Gan Y., Shen Y.H., Wang J., Wang X., Utama B., Wang J., et al. Role of histone deacetylation in cell-specific expression of endothelial nitric-oxide synthase. J Biol Chem 2005, 280(16):16467-16475. 10.1074/jbc.M412960200.
Yan M.S.-C., Matouk C.C., Marsden P.A. Epigenetics of the vascular endothelium. J Appl Physiol 2010, 109(3):916-926. 10.1152/japplphysiol.00131.2010.
Sadr-Nabavi A., Ramser J., Volkmann J., Naehrig J., Wiesmann F., Betz B., et al. Decreased expression of angiogenesis antagonist EFEMP1 in sporadic breast cancer is caused by aberrant promoter methylation and points to an impact of EFEMP1 as molecular biomarker. Int J Cancer 2009, 124(7):1727-1735. 10.1002/ijc.24108.
Ghoshal K., Datta J., Majumder S., Bai S., Kutay H., Motiwala T., et al. 5-Aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 by a proteasomal pathway that requires the KEN box, bromo-adjacent homology domain, and nuclear localization signal. Mol Cell Biol 2005, 25(11):4727-4741. 10.1128/MCB.25.11.4727-4741.2005.
Miller-Kasprzak E., Jagodzinski P.P. 5-Aza-2'-deoxycytidine increases the expression of anti-angiogenic vascular endothelial growth factor 189b variant in human lung microvascular endothelial cells. Biomed Pharmacother 2008, 62(3):158-163. 10.1016/j.biopha.2007.07.015.
Lehnertz B., Ueda Y., Derijck A.A., Braunschweig U., Perez-Burgos L., Kubicek S., et al. Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr Biol 2003, 13(14):1192-1200.
Fuks F., Burgers W.A., Brehm A., Hughes-Davies L., Kouzarides T. DNA methyltransferase Dnmt1 associates with histone deacetylase activity. Nat Genet 2000, 24(1):88-91. 10.1038/71750.
Berger M., Bergers G., Arnold B., Hammerling G.J., Ganss R. Regulator of G-protein signaling-5 induction in pericytes coincides with active vessel remodeling during neovascularization. Blood 2005, 105(3):1094-1101. 10.1182/blood-2004-06-2315.
Bargo S., Raafat A., McCurdy D., Amirjazil I., Shu Y., Traicoff J., et al. Transforming acidic coiled-coil protein-3 (Tacc3) acts as a negative regulator of Notch signaling through binding to CDC10/Ankyrin repeats. Biochem Biophys Res Commun 2010, 400(4):606-612. 10.1016/j.bbrc.2010.08.111.
Miyazaki D., Nakamura A., Fukushima K., Yoshida K., Takeda S., Ikeda S. Matrix metalloproteinase-2 ablation in dystrophin-deficient mdx muscles reduces angiogenesis resulting in impaired growth of regenerated muscle fibers. Hum Mol Genet 2011, 20(9):1787-1799. 10.1093/hmg/ddr062.
Schnaper H.W., Grant D.S., Stetler-Stevenson W.G., Fridman R., D'Orazi G., Murphy A.N., et al. Type IV collagenase(s) and TIMPs modulate endothelial cell morphogenesis in vitro. J Cell Physiol 1993, 156(2):235-246. 10.1002/jcp.1041560204.
Ohno-Matsui K., Uetama T., Yoshida T., Hayano M., Itoh T., Morita I., et al. Reduced retinal angiogenesis in MMP-2-deficient mice. Invest Ophthalmol Vis Sci 2003, 44(12):5370-5375.
Flotho C., Claus R., Batz C., Schneider M., Sandrock I., Ihde S., et al. The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia 2009, 23(6):1019-1028. 10.1038/leu.2008.397.
Iwatsuki K., Tanaka K., Kaneko T., Kazama R., Okamoto S., Nakayama Y., et al. Runx1 promotes angiogenesis by downregulation of insulin-like growth factor-binding protein-3. Oncogene 2005, 24(7):1129-1137. 10.1038/sj.onc.1208287.
Elmasri H., Ghelfi E., Yu C.W., Traphagen S., Cernadas M., Cao H., et al. Endothelial cell-fatty acid binding protein 4 promotes angiogenesis: role of stem cell factor/c-kit pathway. Angiogenesis 2012, 15(3):457-468. 10.1007/s10456-012-9274-0.
Maruo N., Morita I., Shirao M., Murota S. IL-6 increases endothelial permeability in vitro. Endocrinology 1992, 131(2):710-714.
Yang F., Zhang W., Li D., Zhan Q. Gadd45a suppresses tumor angiogenesis via inhibition of the mTOR/STAT3 pathway. J Biol Chem 2013, 10.1074/jbc.M112.418335.
Ebos J.M., Lee C.R., Cruz-Munoz W., Bjarnason G.A., Christensen J.G., Kerbel R.S. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 2009, 15(3):232-239. 10.1016/j.ccr.2009.01.021.
Cui J., Cai X., Zhu M., Liu T., Zhao N. The efficacy of bevacizumab compared with other targeted drugs for patients with advanced NSCLC: a meta-analysis from 30 randomized controlled clinical trials. PLoS One 2013, 8(4):e62038. 10.1371/journal.pone.0062038.
Sennino B., Ishiguro-Oonuma T., Schriver B.J., Christensen J.G., McDonald D.M. Inhibition of c-Met reduces lymphatic metastasis in RIP-Tag2 transgenic mice. Cancer Res 2013, 10.1158/0008-5472.CAN-12-2160.
MacVicar G.R., Hussain M.H. Emerging therapies in metastatic castration-sensitive and castration-resistant prostate cancer. Curr Opin Oncol 2013, 25(3):252-260. 10.1097/CCO.0b013e32835ff161.
Roodhart J.M., Langenberg M.H., Witteveen E., Voest E.E. The molecular basis of class side effects due to treatment with inhibitors of the VEGF/VEGFR pathway. Curr Clin Pharmacol 2008, 3(2):132-143.