Hormone Dependent Cancer

Totonji S., Ramos-Triguero A., Willmann D., Sum M., Urban S., Bauer H. Rieder A., Wang S., Greschik H., Metzger E., Schüle R. (2024). Lysine Methyltransferase 9 (KMT9) Is an Actionable Target in Muscle-Invasive Bladder Cancer. Cancers (Basel). 16(8):1532. doi: 10.3390/cancers16081532.

Wang S., Klein SO., Urban S., Staudt M., Barthes NPF., Willmann D., Bacher J., Sum M., Bauer H., Peng L., Rennar GA., Gratzke C., Schüle KM., Zhang L., Einsle O., Greschik H., MacLeod C., Thomson CG., Jung M., Metzger E., Schüle R. (2024). Structure-guided design of a selective inhibitor of the methyltransferase KMT9 with cellular activity. Nature Communications 15, Article number: 43. doi: 10.1038/s41467-023-44243-6.

Berlin C., Cottard F., Willmann D., Urban S., Tirier SM., Marx L., Rippe K., Schmitt M., Petrocelli V., Greten FR., Fichtner-Feigl S., Kesselring R., Metzger E., Schüle R. (2022). KMT9 Controls Stemness and Growth of Colorectal Cancer. Cancer Res. 15;82(2):210-220. doi: 10.1158/0008-5472.

Frew IJ., Timmers HTM., Schüle R., Gratzke C. (2020 ).The complex genetics of epigenetics in urothelial carcinomas. Nat Rev Urol.  doi: 10.1038/s41585-020-00386-5.

Reiner D., Seifert L., Deck C., Schüle R., Jung M., Stark H. (2020). Epigenetics meets GPCR: inhibition of histone H3 methyltransferase (G9a) and histamine receptor for Prader-Willi Syndrome. Sci Rep. 10(1):13558. doi: 10.1038/s41598-020-70523-y.

Herrlinger EM., Hau M., Redhaber DM., Greve G., Willmann D., Steimle S., Müller M., Lübbert M., Miething CC., Schüle R., Jung M. (2020 ). Nitroreductase-Mediated Release of Inhibitors of Lysine-Specific Demethylase 1 (LSD1) from Prodrugs in Transfected Acute Myeloid Leukaemia Cells. Chembiochem. 21(16):2329-2347. doi: 10.1002/cbic.202000138.

Baumert H.M., Metzger E., Fahrner, M., George J., Thomas R.K., Schilling O. and Schüle R. (2020). Depletion of histone methyltransferase KMT9 inhibits lung cancer cell proliferation by inducing non-apoptotic cell death. Cancer Cell International 20,  doi: 10.1186/s12935-020-1141-2.

Haydn T., Kehr S., Willmann D., Metzger E., Schüle R., Fulda S. (2020). Next-generation sequencing reveals a novel role of lysine-specific demethylase 1 in adhesion of rhabdomyosarcoma cells. Int J Cancer. 146(12):3435-3449. doi: 10.1002/ijc.32806.

Xiong Y., Greschik H., Johansson C., Seifert L., Bacher J., Park KS., Babault N., Martini M., Fagan V., Li F., Chau I., Christott T., Dilworth D., Barsyte-Lovejoy D., Vedadi M., Arrowsmith CH., Brennan P., Fedorov O., Jung M., Farnie G., Liu J., Oppermann U., Schüle R., Jin J. (2019). Discovery of a Potent and Selective Fragment-like Inhibitor of Methyllysine Reader Protein Spindlin 1 (SPIN1). J Med Chem.,  Epub Jul 24, doi: 10.1021/acs.jmedchem.9b00522.

Metzger E., Wang S., Urban S., Willmann D., Schmidt A., Offermann A., Allen A., SumM., Obier N., Cottard F., Ulferts S., Preca B.T., Hermann, B., Maurer J., Greschik H., Hornung V., Einsle O., Perne S., Imhof A., Jung M. and Schüle R. (2019). KMT9 mono-methylates histone H4 Lysine 12 and controls proliferation of prostate cancer cells. Nat. Struct. Mol. Biol. 26, 361-371, doi: 10.1038/s41594-019-0219-9.

Tosic M., Allen A., Willmann D., Lepper C., Kim J., Duteil D., Schüle R. (2018). Lsd1 regulates skeletal muscle regeneration and directs the fate of satellite cells. Nat Commun.  9(1):366. doi: 10.1038/s41467-017-02740-5.

Duteil, D., Tourrette, Y., Eberlin, A., Willmann, D., Patel, D., Friedrichs, N., Müller, J.M. and Schüle, R. (2018). The histone acetyltransferase inhibitor Nir regulates epidermis development. Development 145, doi: 10.1242/dev.158543.

Greschik H., Duteil D., Messaddeq N., Willmann D., Arrigoni L., Sum M., Jung M., Metzger D., Manke T., Günther T., Schüle R. (2017). The histone code reader Spin1 controls skeletal muscle development. Cell Death Dis. 23;8(11):e3173. doi: 10.1038/cddis.2017.468.

Metzger E., Stepputtis S.S., Strietz J., Preca B.T., Urban S., Willmann D., Allen A., Zenk F., Iovino N., Bronsert P., Proske A., Follo M., Boerries M., Stickeler E., Xu J., Wallace M.B., Stafford J.A., Kanouni T., Maurer J., Schüle R. (2017). KDM4 Inhibition Targets Breast Cancer Stem-like Cells. Cancer Res. 77(21):5900-5912. doi: 10.1158/0008-5472

Duteil D., Tosic M., Schüle R. (2017). Lsd1, a metabolic sensor of environment requirements that prevents adipose tissue from aging. Adipocyte 26:1-6. doi: 10.1080/21623945.2017.1345831.

Duteil, D., Tosic, M., Willmann, D., Georgiadi, A., Kanouni, T. and Schüle, R. (2017). Lsd1 prevents age-programed loss of beige adipocytes. PNAS 114(20):5265-5270.

Castex J., Willmann D., Kanouni T., Arrigoni L., Li Y., Friedrich M., Schleicher M., Wöhrle S., Pearson M., Kraut N., Méret M., Manke T., Metzger E., Schüle R., Günther T. (2017). Inactivation of Lsd1 triggers senescence in trophoblast stem cells by induction of Sirt4. Cell Death Dis. 8(2):e2631. doi: 10.1038/cddis.2017.48.

Greschik H, Schüle R, Günther T. (2017). Selective targeting of epigenetic reader domains . Expert Opin Drug Discov. 12(5):449-463. doi: 10.1080/17460441.2017.1303474.

Scionti I., Hayashi S., Mouradian S., Girard E., Esteves de Lima J., Morel V., Simonet T., Wurmser M., Maire P., Ancelin K., Metzger E., Schüle R., Goillot E., Relaix F., Schaeffer L.  (2017). LSD1 Controls Timely MyoD Expression via MyoD Core Enhancer Transcription. Cell Rep. 18(8):1996-2006. doi: 10.1016/j.celrep.2017.01.078.

Haydn T., Metzger E., Schuele R., Fulda S. (2017). Concomitant epigenetic targeting of LSD1 and HDAC synergistically induces mitochondrial apoptosis in rhabdomyosarcoma cells. Cell Death Dis. 8(6):e2879. doi: 10.1038/cddis.2017.239.

Moreno-Juan V., Filipchuk A., Antón-Bolaños N., Mezzera C., Gezelius H., Andrés B., Rodríguez-Malmierca L., Susín R., Schaad O., Iwasato T., Schüle R., Rutlin M., Nelson S., Ducret S., Valdeolmillos M., Rijli F.M., López-Bendito G. Prenatal thalamic waves regulate cortical area size prior to sensory processing (2017). Nat Commun. 8:14172.

Rohde M., Sievers E., Janzer A., Willmann D., Egert A., Schorle H., Schüle R., Kirfel J. (2016). Overexpression of histone demethylase Fbxl10 leads to enhanced migration in mouse embryonic fibroblasts. Exp Cell Res. S0014-4827(16)30265-8.

Duteil D., Tosic M., Lausecker F., L, Nenseth H.Z., Müller J. M., Urban, S., Willmann D., Petroll K., Messaddeq N., Arrigoni L., Manke T., Kornfeld, J.W., Brüning,J.C., Zagoriy V., Meret M., Dengjel J., Kanouni T. and Schüle R. (2016). Lsd1 ablation triggers metabolic reprogramming of brown adipose tissue.  Cell Reports 17: 1008–1021.

Metzger E., Willmann D., McMillan J., Forne I., Metzger P., Gerhardt S., Petroll K., von Maessenhausen A., Urban S., Schott A.K., Espejo A., Eberlin A., Wohlwend D., Schule K.M., Schleicher M., Perner S., Bedford M.T., Jung M., Dengjel J., Flaig R., Imhof A., Einsle O., Schüle R. (2016). Assembly of methylated KDM1A and CHD1 drives androgen receptor-dependent transcription and translocation. Nat. Struct. Mol. Biol. 23(2): 132-139.

Franz H., Greschik H., Willmann D., Ozretic L., Jilg C.A., Wardelmann E., Jung M., Buettner R., Schüle R. (2015). The histone code reader SPIN1 controls RET signaling in liposarcoma. Oncotarget 6 (7): 4773-4789.    

Krönig M., Walter M., Drendel V., Werner M., Jilg C.A., Richter A.S., Backofen R., McGarry D., Follo M., Schultze-Seemann W., Schule R.(2015). Cell type specific gene expression analysis of prostate needle biopsies resolves tumor tissue heterogeneity. Oncotarget. 6 (2): 1302-1314.

Jilg C.A., Ketscher A., Metzger E., Hummel B., Willmann D., Rüsseler V., Drendel V., Imhof A., Jung M., Franz H., Hölz S., Krönig M., Müller J.M., Schüle R. (2014). PRK1/PKN1 controls migration and metastasis of androgen-independent prostate cancer cells. Oncotarget.  5(24), 12646-64.

Ketscher A., Jilg C.A., Willmann D., Hummel B., Imhof A., Rüsseler V., Hölz S., Metzger E, Müller J.M., Schüle R. (2014). LSD1 controls metastasis of androgen-independent prostate cancer cells through PXN and LPAR6. Oncogenesis  3: e120.

Duteil D., Metzger E., Willmann D., Karagianni P., Friedrichs N., Greschik H., Günther T., Buettner R., Talianidis I., Metzger D., Schüle R. (2014). LSD1 promotes oxidative metabolism of white adipose tissue. Nat. Commun. 5:4093.

Zhu, D., Hölz, S., Metzger, E., Pavlovic, M., Jandausch, A., Jilg, C., Galgoczy, P., Herz, C., Moser, M., Metzger, D., Günther, T., Arnold, S.J. and Schüle, R. (2014) Lsd1 regulates differentiation onset and migration of trophoblast stem cells Nat. Commun. 5, 3174-3184.  

Willmann D., Lim S., Wetzel S., Metzger E., Jandausch A., Wilk W., Jung, M., Forne, I., Imhof A., Janzer A., Kirfel, J., Waldmann, H., Schüle, R., Buettner, R. (2012). Impairment of prostate cancer cell growth by a selective and reversible lysine-specific demethylase 1 inhibitor. Int J Cancer. 131, 2704-9.

Metzger E., Imhof A., Patel D., Kahl P., Hoffmeyer K., Friedrichs N., Müller J.M,. Greschik H., Kirfel J., Ji S., Kunowska N., Beisenherz-Huss C., Günther T,. Buettner R., Schüle R. (2010). Phosphorylation of histone H3T6 by PKCbeta(I) controls demethylation at histone H3K4. Nature 464, 792-6.

Metzger E., Yin N., Wissmann M., Kunowska N., Fischer K. Friedrichs N., Patnaik D., Higgins J.M., Potier N., Scheidtmann K.H., Buettner R., Schüle R. (2008). Phosphorylation of histone H3 at threonine 11 establishes a novel chromatin mark for transcriptional regulation. Nat Cell Biol. 10, 53-60.

Wissmann M., Yin N., Mueller J.M., Greschik H., Fodor B.D., Jenuwein T., Vogler C., Schneider R., Guenther T., Buettner R., Metzger E., Schuele R. (2007). Co-operative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression. Nat Cell Biol. 9, 347-353.

Hublitz P., Kunowska N., Mayer U.P., Muller J.M., Heyne K., Yin N., Fritzsche C., Poli C., Miguet L., Schupp I.W., van Grunsven L.A,. Potiers N., van Dorsselaer A., Metzger E., Roemer K., Schuele, R. (2005). NIR is a novel INHAT repressor that modulates the transcriptional activity of p53. Genes Dev. 19, 2912-24.

Metzger E., Wissmann M., Yin N., Muller J.M., Schneider R., Peters A.H., Gunther T., Buettner R., Schuele R. (2005). LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription Nature. 437, 436-439.

Gunther T., Poli C., Muller J.M., Catala-Lehnen P., Schinke T., Yin N., Vomstein S., Amling M., Schuele, R. (2005). Fhl2 deficiency results in osteopenia due to decreased activity of osteoblasts. EMBO J. 24, 3049-56.

Stehlin-Gaon C., Willmann D., Zeyer D., Sanglier S., Van Dorsselaer A., Renaud J.P., Moras D., Schule R. (2003). All-trans retinoic acid is a ligand for the orphan nuclear receptor ROR beta. Nat. Struct. Biol. 10, 820-825.

Metzger E., Muller J.M., Ferrari S., Buettner R., Schuele, R. (2003). A novel inducible transactivation domain in the androgen receptor: implications for PRK in prostate cancer. EMBO J. 15, 270-280.

Mueller J.M., Metzger E., Greschik H., Bosserhoff A.K., Mercep L., Buettner R. and Schuele R. (2002). The transcriptional coactivator FHL2 transmits Rho signals from the cell membrane into the nucleus. EMBO J. 21, 736-748.

Stehlin C., Wurtz J.M., Steinmetz A., Greiner E., Schuele R., Moras D., Renaud J.P. (2001). X-ray structure of the orphan nuclear receptor RORbeta ligand-binding domain in the active conformation. EMBO J. 20, 5822-5831.

Mueller J.M., Isele U., Metzger E., Rempel A., Moser M., Pscherer A., Breyer T., Holubarsch C., Buettner R. and Schuele R. (2000) FHL2, a novel tissue-specific coactivator of the androgen receptor. EMBO J. 19, 359-369.

Schuele R., Pundi R., Kliewer S., Ransone L.J., Bolado J., Yang N., Verma I.M. and Evans R.M. (1990) Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell 62, 1217-1226.    

Schuele R., Umesono K., Mangelsdorf D., Bolado J., Pike W.J. and Evans, R.M. (1990). Jun/Fos and receptors for vitamin A and D recognize a common response element in the human osteocalcin gene. Cell 61, 497-504.   

Schuele R., Muller M., Kaltschmidt Ch. and Renkawitz, R. (1988) Many transcription factors interact synergistically with steroid receptors. Science 242, 1418-1420.