Reversible inhibition of lysine specific demethylase 1 is a novel anti-tumor strategy for poorly differentiated endometrial carcinoma

BMC Cancer

Volumn 14, Issue 1, 2014, Pages

  Theisen, Emily R ^a,b   Gajiwala, Snehal ^a   Bearss, Jared ^a   Sorna, Venkataswamy ^a   Sharma, Sunil ^a,c   Janat Amsbury, Margit ^b,c  

^a UNIVERSITY OF UTAH   (United States)

^b UNIVERSITY OF UTAH   (United States)

^c UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; CASPASE; HCI 2509; HISTONE LYSINE METHYLTRANSFERASE; HISTONE LYSINE METHYLTRANSFERASE INHIBITOR; PROTEIN LSD1; UNCLASSIFIED DRUG; HISTONE; HISTONE DEMETHYLASE; KDM1A PROTEIN, HUMAN;

ANCHORAGE INDEPENDENT GROWTH; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER INHIBITION; CELL CYCLE PROGRESSION; CELL PROLIFERATION; CELL VIABILITY; CONTROLLED STUDY; ENDOMETRIAL CANCER CELL LINE; ENDOMETRIUM CARCINOMA; ENZYME ACTIVATION; FEMALE; GENE INDUCTION; HISTONE METHYLATION; HUMAN; HUMAN CELL; IC50; MOUSE; NICK END LABELING; NONHUMAN; RANDOMIZED CONTROLLED TRIAL; TUMOR DIFFERENTIATION; TUMOR REGRESSION; TUMOR VOLUME; TUMOR XENOGRAFT; ANIMAL; ANTAGONISTS AND INHIBITORS; CANCER GRADING; CELL CYCLE; CELL SURVIVAL; CELL TRANSFORMATION; DISEASE MODEL; DOSE RESPONSE; DRUG EFFECTS; DRUG SCREENING; ENDOMETRIAL NEOPLASMS; METABOLISM; METHYLATION; PATHOLOGY; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL CYCLE; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; CELL TRANSFORMATION, NEOPLASTIC; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; ENDOMETRIAL NEOPLASMS; FEMALE; HISTONE DEMETHYLASES; HISTONES; HUMANS; METHYLATION; MICE; NEOPLASM GRADING; TUMOR BURDEN; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84907954105     PISSN: None     EISSN: 14712407     Source Type: Journal    
DOI: 10.1186/1471-2407-14-752     Document Type: Article

References (52)

1. Siegel R, Naishadham D, Jemal A. Cancer Statistics, 2012. CA Cancer J Clin 2012, 62:10-29. 10.3322/caac.20138, 22237781.
2. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009, 59:225-249. 10.3322/caac.20006, 19474385.
3. National Cancer Institute Endometrial Cancer Home Page http://www.cancer.gov/cancertopics/types/endometrial, National Cancer Institute.
4. Ferlay J, Shin H-R, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2008, 127:2893-2917.
5. Sutton G, Axelrod JH, Bundy BN, Roy T, Homesley HD, Malfetano JH, Mychalczak BR, King ME. Whole abdominal radiotherapy in the adjuvant treatment of patients with stage III and IV endometrial cancer: a gynecologic oncology group study. Gynecol Oncol 2005, 97:755-763. 10.1016/j.ygyno.2005.03.011, 15913742.
6. Bokhman JV. Two pathogenic types of endometrial carcinoma. Gynecol Oncol 1983, 15:10-17. 10.1016/0090-8258(83)90111-7, 6822361.
7. Mendivil A, Schulder KM, Gehrig PA. Non-endometriod adenocarcinoma of the uterine corpus: a review of selected histological subtypes. Cancer Control 2009, 16:46-52.
8. Xiong Y, Dowdy SC, Bosquet JG, Zhao Y, Eberhardt NL, Podratz KC, Jiang S-W. Epigenetic-mediated upregulation of progesterone receptor B gene in endometrial cancer cell lines. Gynecol Oncol 2005, 99:135-141. 10.1016/j.ygyno.2005.05.035, 16024066.
9. Tao MH, Freudenheim JL. DNA methylation in endometrial cancer. Epigenetics 2010, 5:491-498. 10.4161/epi.5.6.12431, 2954259,2954259, 20543579.
10. Friel AM, Zhang L, Curley MD, Therrien VA, Sergent PA, Belden SE, Borger DR, Mohapatra G, Zukerberg LR, Foster R, Rueda BR. Epigenetic regulation of CD133 and tumorgenicity of CD133 positive and negative endometrial cancer cells. Reprod Biol Endocrinol 2010, 8:147. 10.1186/1477-7827-8-147, 3027593, 21122138.
11. Fakhry H, Miyamoto T, Kashima H, Suzuki A, Ke H, Konishi I, Shiozawa T. Immunohistochemical detection of histone deacetylases in endometrial carcinoma: involvement of histone deacetylase 2 in the proliferation of endometrial carcinoma cells. Hum Pathol 2010, 41:848-858. 10.1016/j.humpath.2009.11.012, 20178884.
12. Jiang S, Dowdy SC, Meng XW, Wang Z, Jones MB, Podratz, Jiang S-W. Histone deacetylase inhibitors induce apoptosis in both Type I and Type II endometrical cancer cells. Gynecol Oncol 2007, 105:493-500. 10.1016/j.ygyno.2007.01.012, 3273418, 17303224.
13. Zhou J, Roh J-W, Bandyopadhyay S, Chen Z, Munkarah AR, Hussein Y, Alosh B, Jazaerly T, Hayek K, Semaan A, Sood AK, Ali-Fehmi R. Overexpression of enhancer of zeste homolog 2 (EZH2) and focal adhesion kinase (FAK) in high grade endometrial carcinoma. Gynecol Oncol 2013, 128:344-348. 10.1016/j.ygyno.2012.07.128, 22871469.
14. Eskander RN, Ji T, Huynh B, Wardeh R, Randall LM, Hoang B. Inhibitor of enhancer of zeste homolog 2 (EZH2) expression is associated with decreased tumor cell proliferation, migration, and invasion in endometrial cancer cell lines. Int J Gynecol Cancer 2013, 23:997-1005. 10.1097/IGC.0b013e318296a265, 3694282, 23792601.
15. Le Gallo M, O'Hara AJ, Rudd ML, Urick ME, Hansen NF, O'Neil NJ, Price JC, Zhang S, England BM, Godwin AK, Sgroi DC, Hieter P, Mullikin JC, Merino MJ, Bell DW, . NISC Comparative Sequencing Program Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes. Nat Genet 2012, 44:1310-1315. 10.1038/ng.2455, 3515204, 23104009, NISC Comparative Sequencing Program.
16. Zhao S, Choi M, Overton JD, Bellone S, Roque DM, Cocco E, Guzzo F, English DP, Varughese J, Gasparrini S, Bortolomai I, Buza N, Hui P, Abu-Khalaf M, Ravaggi A, Bignotti E, Bandiera E, Romani C, Todeschini P, Tassi R, Zanotti L, Carrara L, Pecorelli S, Silasi DA, Ratner E, Azodi M, Schwartz PE, Rutherford TJ, Stiegler AL, Mane S, et al. Landscape of somatic single-nucleotide and copy-number mutations in uterine serous carcinoma. Proc Natl Acad Sci U S A 2013, 110:2916-2921. 10.1073/pnas.1222577110, 3581983, 23359684.
17. Le Gallo M, Bell DW. The emerging genomic landscape of endometrial cancer. Clin Chem 2014, 60:98-110. 10.1373/clinchem.2013.205740, 24170611.
18. Dawson MA, Kouzarides T. Cancer epigenetics: from mechanism to therapy. Cell 2012, 150:12-27. 10.1016/j.cell.2012.06.013, 22770212.
19. Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis 2010, 31:27-36. 10.1093/carcin/bgp220, 2802667, 19752007.
20. Stresemann C, Lyko F. Modes of action of the DNA methyltransferase inhibitors azacytidine and decitabine. Int J Cancer 2008, 123:8-13. 10.1002/ijc.23607, 18425818.
21. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 2009, 325:834-840. 10.1126/science.1175371, 19608861.
22. Islam AB, Richter WF, Lopez-Bigas N, Benevolenskaya EV. Selective targeting of histone methylation. Cell Cycle 2011, 10:413-424. 10.4161/cc.10.3.14705, 3115016, 21270517.
23. Popovic R, Licht JD. Emerging epigenetic targets and therapies in cancer medicine. Cancer Discov 2012, 2:405-413. 10.1158/2159-8290.CD-12-0076, 3381982, 22588878.
24. Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 2004, 119:941-953. Ref 19, 10.1016/j.cell.2004.12.012, 15620353.
25. Metzger E, Wissmann M, Yin N, Mueller JM, Schneider R, Peters AHFM, Guenther T, Buettner R, Schuele R. LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature 2005, 437:436-439.
26. Lachner M, O'Sullivan RJ, Jenuwein T. An epigenetic road map for histone lysine methylation. J Cell Sci 2003, 116:2117-2124. 10.1242/jcs.00493, 12730288.
27. Schulte JH, Lim S, Schramm A, Friedrichs N, Koster J, Versteeg R, Ora I, Pajtler K, Klein-Hitpass L, Kuhfittig-Kulle S, Metzger E, Schüle R, Eggert A, Buettner R, Kirfel J. Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma: implications for therapy. Cancer Res 2009, 69:2065-2071.
28. Harris WJ, Huang X, Lynch JT, Spencer GJ, Hitchin JR, Li Y, Ciceri F, Blaser JG, Greystoke BF, Jordan AM, Miller CJ, Ogilvie DJ, Somervaille TC. The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells. Cancer Cell 2012, 21:473-487. 10.1016/j.ccr.2012.03.014, 22464800.
29. Lim S, Janzer A, Becker A, Zimmer A, Schüle R, Buettner R, Kirfel J. Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology. Carcinogenesis 2010, 31:512-520. 10.1093/carcin/bgp324, 20042638.
30. Kahl P, Gullotti L, Heukamp LC, Wolf S, Friedrichs N, Vorreuther R, Solleder G, Bastian PJ, Ellinger J, Metzger E, Schüle R, Buettner R. Androgen receptor coactivators lysine-specific histone demethylase 1 and four and a half LIM domain protein 2 predict risk of prostate cancer recurrence. Cancer Res 2006, 66:11341-11347. 10.1158/0008-5472.CAN-06-1570, 17145880.
31. Hayami S, Kelly JD, Cho HS, Yoshimatsu M, Unoki M, Tsunoda T, Field HI, Neal DE, Yamaue H, Ponder BA, Nakamura Y, Hamamoto R. Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers. Int J Cancer 2011, 128:574-586. 10.1002/ijc.25349, 20333681.
32. Zhao ZK, Yu HF, Wang DR, Dong P, Chen L, Wu WG, Ding WJ, Liu YB. Overexpression of lysine specific demethylase 1 predicts worse prognosis in primary hepatocellular carcinoma patients. World J Gastroenterol 2012, 18:6651-6656. 10.3748/wjg.v18.i45.6651, 3516205, 23236241.
33. Schildhaus HU, Riegel R, Hartmann W, Steiner S, Wardelmann E, Merkelbach-Bruse S, Tanaka S, Sonobe H, Schüle R, Buettner R, Kirfel J. Lysine-specific demethylase 1 is highly expressed in solitary fibrous tumors, synovial sarcomas, rhabdomyosarcomas, desmoplastic small round cell tumors, and malignant peripheral nerve sheath tumors. Hum Pathol 2011, 42:1667-1675. 10.1016/j.humpath.2010.12.025, 21531005.
34. Bennani-Baiti I-M, Machado I, Llombart-Bosch A, Kovar H. Lysine-specific demethylase 1 (LSD1/KDM1A/AOF2/BHC110) is expressed and is an epigenetic drug target in chondrosarcoma, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma. Hum Pathol 2012, 43:1300-1307. 10.1016/j.humpath.2011.10.010, 22245111.
35. Sorna V, Theisen ER, Stephens B, Warner SL, Bearss DJ, Vankayalapati H, Sharma S. High-throughput virtual screening identifies novel N'-(1-phenylethylidene)-benzohydrazides as potent, specific, and reversible inhibitors of LSD1. J Med Chem 2013, 56:9496-9508. 10.1021/jm400870h, 24237195.
36. Stephens BJ, Theisen ER, Warner SL, Sharma S, Bearss DJ. Abstract 1045: Activity of the LSD1 inhibitor HCI-2509 in ER-negative breast cancer cells. Proceedings of the American Association for Cancer Research 103rd Annual Meeting 2012: 31 March -4 April 2012 2012, Chicago, IL.
37. Theisen ER, Bearss J, Sorna V, Bearss DJ, Sharma S. Abstract 3: Targeted inhibition of LSD1 in castration-resistant prostate cancer. Proceedings of the American Association for Cancer Research 104th Annual Meeting 2013 2013, Washington, DC, 6-10 April 2013.
38. Sankar S, Theisen ER, Bearss J, Mulvihill T, Hoffman LM, Sorna V, Beckerle MC, Sharma S, Lessnick SL. LSD1 inhibition interferes with global EWS/ETS transcriptional activity and impedes Ewing sarcoma tumor growth. Clin Cancer Res 2014, 20:4584-4597. 10.1158/1078-0432.CCR-14-0072, 24963049.
39. Lessnick SL, Dacwag CS, Golub TR. The Ewing's sarcoma oncoprotein EWS/FLI induces a p53-dependent growth arrest in primary human fibroblasts. Cancer Cell 2002, 1:393-401. 10.1016/S1535-6108(02)00056-9, 12086853.
40. Nakamura M, Kyo S, Zhang B, Zhang X, Mizumoto Y, Takakura M, Maida Y, Mori N, Hashimoto M, Ohno S, Inoue M. Prognostic impact of CD133 expression as a tumor-initiating cell marker in endometrial cancer. Hum Pathol 2010, 41:1516-1529. 10.1016/j.humpath.2010.05.006, 20800872.
41. McDonald OG, Wu H, Timp W, Doi A, Feinberg AP. Genome-scale epigenetic reprogramming during epithelial-mesenchymal transition. Nat Struct Mol Biol 2011, 18:867-874. 10.1038/nsmb.2084, 3150339, 21725293.
42. Lin T, Ponn A, Hu X, Law BK, Lu J. Requirement of the histone demethylase LSD1 in Snai1-mediated transcriptional repression during epithelial-mesenchymal transition. Oncogene 2010, 29:4896-4904. 10.1038/onc.2010.234, 3093107, 20562920.
43. Llobet D, Pallares J, Yeramian A, Santacana M, Eritja N, Velasco A, Dolcet X, Matias-Guiu X. Molecular pathology of endometrial carcinoma: practical aspects from the diagnostic and therapeutic viewpoints. J Clin Pathol 2009, 62:777-785. 10.1136/jcp.2008.056101, 18977806.
44. Limpert E, Stahel WA, Abbt M. Log-normal distributions across the sciences: keys and clues. Bioscience 2001, 51:341-352.
45. Sankar S, Bell R, Stephens B, Zhuo R, Sharma S, Bearss DJ, Lessnick SL. Mechanism and relevance of EWS/FLI-mediated transcriptional repression in Ewing sarcoma. Oncogene 2013, 32:5089-5100. 10.1038/onc.2012.525, 3899696, 23178492.
46. Wang Y, Zhang H, Chen Y, Sun Y, Yang F, Yu W, Liang J, Sun L, Yang X, Shi L, Li R, Li Y, Zhang Y, Li Q, Yi X, Shang Y. LSD1 is a subunit of the NuRD complex and targets the metastasis programs in breast cancer. Cell 2009, 138:660-672. 10.1016/j.cell.2009.05.050, 19703393.
47. Wei Y, Xia W, Zhang Z, Liu J, Wang H, Adsay NV, Albarracin C, Yu D, Abbruzzese JL, Mills GB, Bast RC, Hortobagyi GN, Hung MC. Loss of trimethylation at lysine 27 of histone H3 is a predictor of poor outcome in breast, ovarian, and pancreatic cancers. Mol Carcinog 2008, 47:701-706. 10.1002/mc.20413, 2580832, 18176935.
48. Nair VD, Ge Y, Balasubramaniyan N, Kim J, Okawa Y, Chikina M, Troyanskaya O, Sealfon SC. Involvement of histone demethylase LSD1 in short-time-scale gene expression changes during cell cycle progression in embryonic stem cells. Mol Cell Biol 2012, 32:4861-4876. 10.1128/MCB.00816-12, 3497594, 23028048.
49. Yin F, Lan R, Zhang X, Zhu L, Chen F, Xu Z, Liu Y, Ye T, Sun H, Lu F, Zhang H. LSD1 regulates pluripotency of embryonic stem/carcinoma cells through histone deacetylase 1-mediated deacetylation of histone H4 at lysine 16. Mol Cell Biol 2014, 34:158-179. 10.1128/MCB.00631-13, 3911295, 24190971.
50. Scoumanne A, Chen X. The lysine-specific demethylase 1 is required for cell proliferation in both p53-dependent and -independent manners. J Biol Chem 2007, 282:15471-15475. 10.1074/jbc.M701023200, 17409384.
51. Cho HS, Suzuki T, Dohmae N, Hayami S, Unoki M, Yoshimatsu M, Toyokawa G, Takawa M, Chen T, Kurash JK, Field HI, Ponder BA, Nakamura Y, Hamamoto R. Demethylation of RB regulator MYPT1 by histone demethylase LSD1 promotes cell cycle progression in cancer cells. Cancer Res 2011, 71:655-660. 10.1158/0008-5472.CAN-10-2446, 21115810.
52. Lum DH, Matsen C, Welm AL, Welm BE. Overview of human primary tumorgraft models: comparisons with traditional oncology preclinical models and the clinical relevance and utility of primary tumorgrafts in basic and translational oncology research. Curr Protoc Pharmacol 2012, Chapter 14:Unit 14.22. 3539738, 23258598.