Partners in crime: STAT3 and CDK6 control transformation in hematopoietic cells

NETWORK CONTRIBUTION

We propose a novel mode by which STAT3 regulates the chromatin landscape in transformed haematopoietic cells in cooperation with the cell cycle regulator CDK6. We shall test this notion by means of BCR ABL+ and NPM-ALK+ tumours. If either STAT3 or CDK6 is absent, tumour formation is severely reduced. Our preliminary studies suggest a tight interaction of STAT3 and CDK6 on chromatin, which we intend to investigate further. Our investigations will include the STAT3 mutations that have been repeatedly found in human lymphoid malignancies. These clinically relevant STAT3 mutations will be studied in model cell lines and in vitro and in vivo in B and T lymphoid cells.

Our major goal is to test the ability of lymphocytes to propagate leukaemia, their epigenetic landscape and their interaction with CDK6. The work should reveal a novel layer of regulation of STAT3, mediated via its interaction with CDK6 and might open a novel therapeutic avenue to interfere with STAT3´s function.

Within the proposed project we aim to determine the stepwise cooperativity of STAT3 and TFs in gene induction and histone modification.

CONTACT

Institut für Pharmakologie und Toxikologie
Department für Biomedizinische Wissenschaften
Veterinärmedizinische Universität Wien

Veterinärplatz 1
A-1210 Vienna
Austria

veronika.sexl@vetmeduni.ac.at

PUBLICATIONS

SFB-F61 / F28 related publications - Group Sexl

Hoelbl, A., Kovacic, B., Kerenyi, M.A., Simma, O., Warsch, W., Cui, Y., Beug, H., Hennighausen, L., Moriggl, R. and Sexl, V. (2006).
Clarifying the role of Stat5 in lymphoid development and Abelson-induced transformation.
Blood 107:4898-906. doi: 10.1182/blood-2005-09-3596
Kovacic, B., Stoiber, D., Moriggl, R., Weisz, E., Ott, R. G., Kreibich, R., Levy, D.E., Beug, H., Freissmuth, M., and Sexl, V. (2006).
STAT1 acts as a tumor promoter for leukemia development.
Cancer Cell 10:77-87.
Ott, R.G., Simma, O., Kollmann, K., Weisz, E., Zebedin, E.M., Schorpp-Kistner, M., Heller, G., Zochbauer, S., Wagner, E.F., Freissmuth, M. and Sexl, V. (2007).
Jun B is a gatekeeper for B-lymphoid leukemia.
Oncogene 26:4863-71. doi: 10.1038/sj.onc.1210285
Staber, P.B., Vesely, P., Haq, N., Ott, R.G., Funato, K., Bambach, I., Fuchs, C., Schauer, S., Linkesch, W., Hrzenjak, A., Dirks, W.G., Sexl, V., Bergler, H., Kadin, M.E., Sternberg, D.W., Kenner, L. and Hoefler, G. (2007).
The oncoprotein NPM-ALK of anaplastic large cell lymphoma induces JUNB transcription via ERK1/2 abd JunB translation via mTOR signaling.
Blood 110:3374-83. doi: http://dx.doi.org/10.1182/blood-2007-02-071258
Mayerhofer, M., Gleixner, K.V., Hoelbl, A., Florian, S., Hoermann, G., Aichberger, K.J., Bilban, M., Esterbauer, H., Krauth, M.T., Sperr, W.R., Longley, J.B., Kralovic, R., Moriggl, R., Zappulla, J., Liblau, R.S., Schwarzinger, I., Sexl, V., Sillaber, C. and Valent, P. (2008).
Unique effects of KIT D816V in BaF3 cells: induction of cluster formation, histamine synthesis, and early mast cell differentiation antigens.
J Immunol 180:5466-76. doi: 10.4049/jimmunol.180.8.5466
Schuster, C., Müller, M., Freissmuth, M., Sexl, V. and Stoiber, D. (2008).
Commentary on H.Ide et al: “Tyk2 expression and its signaling enhances invasiveness of prostate cancer cells”.
Biochem Biophys Res Commun 366:869-70. doi: 10.1016/j.bbrc.2007.12.017
Kornfeld, J.W., Grebien, F., Kerenyi, M.A., Friedbichler, K., Kovacic, B., Zankl, B., Hoelbl, A., Nivarti, H., Beug, H., Sexl, V., Müller, M., Kenner, L., Müllner, E.W., Gouilleux, F. and Moriggl, R. (2008).
The different functions of Stat5 and chromatin alteration through Stat5 proteins.
Front Biosci 13:6237-54. [review] doi: dx.doi.org/10.2741/3151
Mayerhofer, M., Gleixner, K.V., Mayerhofer, J., Hoermann, G., Jaeger, E., Aichberger, K.J., Ott, R.G., Greish, K., Nakamura, H., Derdak, S., Samorapoompichit, P., Pickl, W.F., Sexl, V., Esterbauer, H., Schwarzinger, I., Sillaber, C., Maeda, H. and Valent, P. (2008).
Targeting of heat shock protein 32 (Hsp 32)/heme oxygenase-1 (HO-1) in leukemic cells in chronic myleoid leukemia. A novel approach to overcome resistance against imatinib.
Blood 111:2200-14. doi: http://dx.doi.org/10.1182/blood-2006-11-055723
Zebedin, E., Simma, O., Schuster, C., Putz, E.M., Fajmann, S., Warsch, W., Eckelhart, E., Stoiber, D., Weisz, E., Schmid, J.A., Pickl, W.F., Baumgartner, C., Valent, P., Piekorz, R.P., Freissmuth, M. and Sexl, V. (2008).
Leukemic challenge unmasks a requirement for PI3Kdelta in NK cell-mediated tumor surveillance.
Blood 112:4655-64. doi: 10.1182/blood-2008-02-139105
Pilz, A., Kratky, W., Stockinger, S., Simma, O., Kalinke, U., Lingnau, K., von Gabain, A., Stoiber, D., Sexl, V., Kolbe, T., Rulicke, T., Müller, M. and Decker, T. (2009).
Dendritic cells require STAT-1 phosphorylated at its transactivating domain for the induction of peptide-specific CTL.
J Immunol 183:2286-93. doi: 10.4049/jimmunol.0901383
Simma, O., Zebedin, E., Neugebauer, N., Schellack, C., Pilz, A., Chang-Rodriguez, S., Lingnau, K., Weisz, E., Putz, E.M., Pickl, W.F., Felzmann, T., Müller, M., Decker, T., Sexl, V. and Stoiber, D. (2009).
Identification of an indispensable role for tyrosine kinase 2 in CTL-mediated tumor surveillance.
Cancer Res 69:203-11. doi: 10.1158/0008-5472.CAN-08-1705
Ecker, A., Simma, O., Hoelbl, A., Kenner, L., Beug, H., Moriggl, R. and Sexl, V. (2009).
The dark and the bright side of Stat3: proto-oncogene and tumor-suppressor.
Front Biosci 14:2944-58. [review] doi: dx.doi.org/10.2741/3425
Hoelbl*, A., Schuster*, C., Kovacic, B., Zhu, B., Wickre, M., Hoelzl, M.A., Fajmann, S., Grebien, F., Warsch, W., Stengl, G., Hennighausen, L., Poli, V., Beug†, H., Moriggl, R., and Sexl, V. (2010). *equal contribution †1945-2011, SFB member of the 1st funding period; associated with coordination project
Stat5 is indispensable for the maintenance of bcr/abl-positive leukaemia.
EMBO Mol Med 2: 98-110. doi: 10.1002/emmm.201000062
Beer-Hammer, S., Zebedin, E., von Holleben, M., Alferink, J., Reis, B., Dresing, P., Degrandi, D., Scheu, S., Hirsch, E., Sexl, V., Pfeffer, K., Nurnberg, B., and Piekorz, R.P. (2010).
The catalytic PI3K isoforms F28110gamma and F28110delta contribute to B cell development and maintenance, transformation, and proliferation.
J Leukoc Biol 87: 1083-1095. doi: 10.1189/jlb.0809585
Eckelhart, E., Warsch, W., Zebedin, E., Simma, O., Stoiber, D., Kolbe, T., Rulicke, T., Mueller, M., Casanova, E., and Sexl, V. (2011).
A novel Ncr1-Cre mouse reveals the essential role of STAT5 for NK cell survival and development.
Blood 117: 1565-1573. doi: dx.doi.org/10.1182/blood-2010-06-291633
Kornfeld, J.W., Isaacs, A., Vitart, V., Pospisilik, J.A., Meitinger, T., Gyllensten, U., Wilson, J.F., Rudan, I., Campbell, H., Penninger, J.M., Sexl, V., Moriggl, R., van Duijn, C., Pramstaller, P.P., and Hicks, A.A. (2011).
Variants in STAT5B Associate with Serum TC and LDL-C Levels.
J Clin Endocrinol Metab. 96: E1496-501. doi: dx.doi.org/10.1210/jc.2011-0322
Mueller, K.M., Kornfeld, J.W., Friedbichler, K., Blaas, L., Egger, G., Esterbauer, H., Hasselblatt, P., Schlederer, M., Haindl, S., Wagner, K.U., Engblom, D., Haemmerle, G., Kratky, D., Sexl, V., Kenner, L., Kozlov, A.V., Terracciano, L., Zechner, R., Schuetz, G., Casanova, E., Pospisilik, J.A., Heim, M.H., and Moriggl, R. (2011).
Impairment of hepatic growth hormone and glucocorticoid receptor signaling causes steatosis and hepatocellular carcinoma in mice.
Hepatology 54: 1398-1409. doi: 10.1002/hep.24509
Schneckenleithner, C., Bago-Horvath, Z., Dolznig, H., Neugebauer, N., Kollmann, K., Kolbe, T., Decker, T., Kerjaschki, D., Wagner, K.-U., Müller, M., Stoiber, D., and Sexl, V. (2011).
Putting the brakes on mammary tumorigenesis: Loss of STAT1 predisposes to intraepithelial neoplasias.
Oncotarget 2: 1043-1054. online ISSN: 1949-2553
Schuster*, C., Berger*, A., Hoelzl, M.A., Putz, E.M., Frenzel, A., Simma, O., Moritz, N., Hoelbl, A., Kovacic, B., Freissmuth, M., Müller, M., Villunger, A., Mullauer, L., Schmatz, A.I., Streubel, B., Porpaczy, E., Jager, U., Stoiber, D., and Sexl, V. (2011). *equal contribution
The cooperating mutation or "second hit" determines the immunological visibility towards MYC-induced murine lymphomas.
Blood 118: 4635-4645. doi: http://dx.doi.org/10.1182/blood-2010-10-313098

Warsch, W., Kollmann, K., Eckelhart, E., Fajmann, S., Cerny-Reiterer, S., Holbl, A., Gleixner, K.V., Dworzak, M., Mayerhofer, M., Hoermann, G., Herrmann, H., Sillaber, C., Egger, G., Valent, P., Moriggl, R., and Sexl, V. (2011).
High STAT5 levels mediate imatinib resistance and indicate disease progression in chronic myeloid leukemia.
Blood 117: 3409-3420. doi: http://dx.doi.org/10.1182/blood-2009-10-248211
Friedbichler, K., Hoelbl, A., Li, G., Bunting, K.D., Sexl, V., Gouilleux, F., and Moriggl, R. (2011).
Serine phosphorylation of the Stat5a C-terminus is a driving force for transformation.
Front Biosci 17: 3043-3056. [review] doi: http://dx.doi.org/10.2741/3897
Strobl, B., Stoiber, D., Sexl, V., and Müller, M. (2011).
Tyrosine kinase 2 (Tyk2) in cytokine signalling and host immunity.
Front Biosci 17: 3224-3232. [review] doi: http://dx.doi.org/10.2741/3908
Kollmann, K., Heller, G., Ott, R.G., Scheicher, R., Zebedin-Brandl, E., Schneckenleithner, C., Simma, O., Warsch, W., Eckelhart, E., Hoelbl, A., Bilban, M., Zochbauer-Muller, S., Malumbres, M., and Sexl, V. (2011).
C-JUN promotes BCR-ABL induced lymphoid leukemia by inhibiting methylation of the 5' region of Cdk6.
Blood 117: 4065-4075. doi: dx.doi.org/10.1182/blood-2010-07-299644
Laimer, D., Dolznig, H., Kollmann, K., Vesely, P.W., Schlederer, M., Merkel, O., Schiefer, A.-I., Hassler, M.R., Heider, S., Amenitsch, L., Thallinger, C., Staber, P.B., Simonitsch-Klupp, I., Artaker, M., Lagger, S., Pileri, S., Piccaluga, P.P., Valent, P., Messana, K., Landra, I., Weichhart, T., Knapp, S., Shehata, M., Todaro, M., Sexl, V., Höfler, G., Piva, R., Medico, E., Riggeri, B.A., Cheng, M., Eferl, R., Egger, G., Penninger, J.M., Jaeger, U., Moriggl, R., Inghirami, G., and Kenner, L. (2012).
PDGFR blockade is a rational and effective therapy for NPM-ALK–driven lymphomas.
Nat Med 18: 1699-1704. doi: 10.1038/nm.2966
Putz*, E.M., Prchal-Murphy*, M., Simma, O.A., Forster, F., Koenig, X., Stockinger, H., Piekorz, R.P., Freissmuth, M., Müller, M., Sexl, V., and Zebedin-Brandl, E. (2012). *equal contribution
PI3Kδ Is Essential for Tumor Clearance Mediated by Cytotoxic T Lymphocytes.
PLoS One 7: e40852. doi: 10.1371/journal.pone.0040852
Warsch, W., Grundschober, E., Berger, A., Gille, L., Cerny-Reiterer, S., Tigan, A.-S., Hoelbl-Kovacic, A., Valent, P., Moriggl, R., and Sexl, V. (2012).
STAT5 triggers BCR-ABL1 mutation by mediating ROS production in chronic myeloid leukaemia.
Oncotarget 3: 1669-1687. online ISSN: 1949-2553
Kernbauer, E., Maier, V., Stoiber, D., Strobl, B., Schneckenleithner, C., Sexl, V., Reichart, U., Kalinke, U., Reizis, B., Jamieson, A., Müller, M., and Decker, T. (2012).
Conditional Stat1 ablation reveals the importance of interferon signaling for immunity to Listeria monocytogenes infection.
PLoS Pathog 8: e1002763. doi: 10.1371/journal.ppat.1002763
Kovacic, B., Hoelbl, A., Litos, G., Alacakaptan, M., Schuster, C., Fischhuber, K.M., Kerenyi, M.A., Stengl, G., Moriggl, R., Sexl, V., and Beug†, H. (2012). †1945-2011, SFB member of the 1st funding period; associated with coordination project
Diverging fates of cells of origin in acute and chronic leukaemia.
EMBO Mol Med 4: 283-297. doi: 10.1002/emmm.201100208
Mizutani*, T., Neugebauer*, N., Putz*, E.M., Moritz, N., Simma, O., Zebedin-Brandl, E., Gotthardt, D., Warsch, W., Eckelhart, E., Kantner, H.-P., Kalinke, U., Lienenklaus, S., Weiss, S., Strobl, B., Müller, M., Sexl, V., and Stoiber, D. (2012). *equal contribution
Conditional IFNAR1 ablation reveals distinct requirements of Type I IFN signaling for NK cell maturation and tumor surveillance.
Oncoimmunology 1: 1027-1037. doi: 10.4161/onci.21284
Hantschel*, O., Warsch*, W., Eckelhart, E., Kaupe, I., Grebien, F., Wagner, K.U., Superti-Furga, G., and Sexl, V. (2012). *equal contribution
BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic myeloid leukemia.
Nat Chem Biol 8: 285-293. doi: 10.1038/nchembio.775
Putz, E.M., Zebedin, E., and Sexl, V. (2012).
STAT Transcription Factors: Controlling All Aspects of NK Cell Biology.
In Jak-Stat Signaling: From Basics to Disease (Decker, T. and Müller, M., Eds.) Springer Wien Heidelberg New York Dordrecht London. pp. 187-204. [book chapter] doi: 10.1007/978-3-7091-0891-8_12 ISBN: 978-3-7091-0890-1
Kollmann, K., Heller, G., Schneckenleitner, C., Warsch, W., Scheicher, R., Ott, R.G., Schäfer, M., Fajmann, S., Schlederer, M., Schiefer, A.-I., Reichart, U., Mayerhofer, M., Hoeller, C., Zöchbauer-Müller, S., Kerjaschki, D., Bock, C., LKenner, L., Hoefler, G., Freissmuth, M., Green, A.R., Moriggl, R., Busslinger, M., Malumbres, M., and Sexl, V. (2013).
A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis.
Cancer Cell 24: 167-181. doi: dx.doi.org/10.1016/j.ccr.2013.07.012
Köprülü, A.D., Kastner, R., Wienerroither, S., Lassnig, C., Putz, E.-M., Majer, O., Reutterer, B., Sexl, V., Kuchler, K., Müller, M., Decker, T., and Ellmeier, W. (2013).
The tyrosine kinase Btk regulates the macrophage response to Listeria monocytogenes infection.
PLoS One 8: e60476. doi: 10.1371/journal.pone.0060476
Putz, E.M., Gotthardt, D., Hoermann, G., Csiszar, A., Wirth, S., Berger, A., Straka, E., Rigler, D., Wallner, B., Jamieson, A.M., Pickl, W.F., Zebedin-Brandl, E.M., Müller, M., Decker, T., and Sexl, V. (2013).
CDK8-Mediated STAT1-S727 Phosphorylation Restrains NK Cell Cytotoxicity and Tumor Surveillance.
Cell Rep 15: 437-444. doi: 10.1016/j.celrep.2013.07.012
Hannesdottir, L., Tymoszuk, P., Parajuli, N., Wasmer, M.H., Philipp, S., Daschil, N., Datta, S., Koller, J.B., Tripp, C.H., Stoitzner, P., Muller-Holzner, E., Wiegers, G.J., Sexl, V., Villunger, A., and Doppler, W. (2013).
Lapatinib and doxorubicin enhance the Stat1-dependent antitumor immune response.
Eur J Immunol. 43: 2718-2729. doi: 10.1002/eji.201242505
Kantner*, H.P., Warsch*, W., Delogu, A., Bauer, E., Esterbauer, H., Casanova, E., Sexl, V., and Stoiber, D. (2013). *equal contribution
ETV6/RUNX1 Induces Reactive Oxygen Species and Drives the Accumulation of DNA Damage in B Cells.
Neoplasia 15: 1292-1300. doi: 10.1593/neo.131310
Richter, K., Perriard, G., Behrendt, R., Schwendener, R.A., Sexl, V., Dunn, R., Kamanaka, M., Flavell, R.A., Roers, A., and Oxenius, A. (2013).
Macrophage and T cell produced IL-10 promotes vrial chronicity.
PLoS Pathog 9: e1003735. doi: 10.1371/journal.ppat.1003735
Warsch, W., Grundschober, E., and Sexl, V. (2013).
Adding a new facet to STAT5 in CML: Multitasking for leukemic cells.
Cell Cycle 12: 1813-1814. [editorial feature] doi: 10.4161/cc.25116
Warsch, W., Walz, C., and Sexl, V. (2013).
JAK of all trades: JAK2-STAT5 as novel therapeutic targets in BCR-ABL1+ chronic myeloid leukemia.
Blood 122: 2167-2175. doi: dx.doi.org/10.1182/blood-2013-02-485573
Koromilas, A.E., and Sexl, V. (2013).
The tumor suppressor function of STAT1 in breast cancer.
JAK-STAT 2:2, 1-5. [review] doi: 10.4161/jkst.23353
Berger*, A., Hoelbl-Kovacic*, A., Bourgeais, J., Hoefling, L., Warsch, W., Grundschober, E., Uras, I.Z., Menzl, I., Putz, E.M., Hoermann, G., Schuster, C., Fajmann, S., Leitner, E., Kubicek, S., Moriggl, R., Gouilleux, F., and Sexl, V. (2014). *equal contribution
PAK-dependent STAT5 serine phosphorylation is required for BCR-ABL-induced leukemogenesis.
Leukemia 28: 629-641. doi: 10.1038/leu.2013.351
Berger, A., Sexl, V., Valent, P., and Moriggl, R. (2014).
Inhibition of STAT5: A therapeutic option in BCR-ABL1-driven leukemia.
Oncotarget 5: 9564-9576. Online ISSN: 1949-2553
Gotthardt, D., Putz, E.M., Straka, E., Kudweis, P., Biaggio, M., Poli, V., Strobl, B., Müller, M., and Sexl, V. (2014).
Loss of STAT3 in murine NK cells enhances NK cell-dependent tumor surveillance.
Blood 124: 2370-2379. doi: http://dx.doi.org/10.1182/blood-2014-03-564450
Kovacic, B., Hoelbl-Kovacic, A., Fischhuber, K.M., Leitner, N.R., Gotthardt, D., Casanova, E., Sexl, V., and Müller, M. (2014).
Lactotransferrin-Cre reporter mice trace neutrophils, monocytes/macrophages and distinct subtypes of dendritic cells.
Haematologica 99: 1006-1015. doi: 10.3324/haematol.2013.097154
Gotthardt, D., Prchal-Murphy, M., Seillet, C., Glasner, A., Mandelboim, O., Carotta, S., Sexl, V., and Putz, E.M. (2014).
NK cell development in bone marrow and liver: site matters.
Genes Immun 15: 584-587. doi: 10.1038/gene.2014.55
Grundschober, E., Hoelbl-Kovacic, A., Bhagwat, N., Kovacic, B., Scheicher, R., Eckelhart, E., Kollmann, K., Keller, M., Grebien, F., Wagner, K.U., Levine, R.L., and Sexl, V. (2014).
Acceleration of Bcr-Abl leukemia induced by deletion of JAK2.
Leukemia 28: 1918-1922. doi: 10.1038/leu.2014.152
Putz, E.M., Hoelzl, M.A., Baeck, J., Bago-Horvath, Z., Schuster, C., Reichholf, B., Kern, D., Aberger, F., Sexl, V., and Hoelbl-Kovacic, A. (2014).
Loss of STAT3 in Lymphoma Relaxes NK Cell-Mediated Tumor Surveillance.
Cancers 6: 193-210. doi: 10.3390/cancers6010193
Klose, C.S., Flach, M., Mohle, L., Rogell, L., Hoyler, T., Ebert, K., Fabiunke, C., Pfeifer, D., Sexl, V., Fonseca-Pereira, D., Domingues, R.G., Veiga-Fernandes, H., Arnold, S.J., Busslinger, M., Dunay, I.R., Tanriver, Y., and Diefenbach, A. (2014).
Differentiation of Type 1 ILCs from a Common Progenitor to All Helper-like Innate Lymphoid Cell Lineages.
Cell 157: 340-356.
Pathria*, P., Gotthardt*, D., Prchal-Murphy*, M., Putz*, E.M., Holcmann, M., Schlederer, M., Grabner, B., Crncec, I., Svinka, J., Musteanu, M., Hoffmann, T., Filipits, M., Berger, W., Poli, V., Kenner, L., Bilban, M., Casanova, E., Müller, M., Strobl, B., Bayer, E., Mohr, T., Sexl, V., and Eferl§, R. (2015). *equal contribution §SFB member of the 1st and 2nd funding period
Myeloid STAT3 promotes formation of colitis-associated colorectal cancer in mice.
Oncoimmunology 4(4):e998529. doi: 10.1080/2162402X.2014.998529
Prchal-Murphy, M., Witalisz-Siepracka, A., Bednarik, K.T., Putz, E.M., Gotthardt, D., Meissl, K., Sexl, V., Müller, M., and Strobl, B. (2015).
In vivo tumor surveillance by NK cells requires TYK2 but not TYK2 kinase activity.
Oncoimmunology. doi: 10.1080/2162402X.2015.1047579
Schneckenleithner, C., Hoelbl-Kovacic, A., and Sexl, V. (2015).
Modeling BCR/ABL-Driven Malignancies in the Mouse.
Methods in Mol Biol 1267: 263-282. [review] doi: 10.1007/978-1-4939-2297-0_12
Bottos, A., Gotthardt, D., Gill, J.W., Gattelli, A., Frei, A., Tzankov, A., Sexl, V., Wodnar-Filipowicz, A., and Hynes, N.E. (2016).
Decreased NK-cell tumour immunosurveillance consequent to JAK inhibition enhances metastasis in breast cancer models.
Nat Commun 7, 12258.
Gotthardt, D., Putz, E.M., Grundschober, E., Prchal-Murphy, M., Straka, E., Kudweis, P., Heller, G., Bago-Horvath, Z., Witalisz-Siepracka, A., Cumaraswamy, A.A., Gunning, P.T., Strobl, B., Muller, M., Moriggl, R., Stockmann, C., and Sexl, V. (2016).
STAT5 is a key regulator in NK cells and acts as molecular switch from tumor surveillance to tumor promotion.
Cancer discovery 6, 414-429
Klose, R., Krzywinska, E., Castells, M., Gotthardt, D., Putz, E.M., Kantari-Mimoun, C., Chikdene, N., Meinecke, A.K., Schrodter, K., Helfrich, I., Fandrey, J., Sexl, V., and Stockmann, C. (2016).
Targeting VEGF-A in myeloid cells enhances natural killer cell responses to chemotherapy and ameliorates cachexia.
Nat Commun 7, 12528
Majoros, A., Platanitis, E., Szappanos, D., Cheoan, H.J., Vogl, C., Shukla, P., Stark, G.R., Sexl, V., Schreiber, R.D., Schindler, C., Müller, M., and Decker, T. (2016).
Response to interferons and antibacterial innate immunity in absence of tyrosine-phosphorylated STAT1.
EMBO Rep 17, 367-382
Putz, E.M., Majoros, A., Gotthart, D., Prchal-Murphy, M., Zebedin-Brandl, E., Fux, D.A., Schlattl, A., Schreiber, R.D., Carotta, S., Müller, M., Gerner, C., Decker, T., and Sexl, V. (2016).
Novel non-­canonical role of STAT1 in Natural Killer cell cytotoxicity.
OncoImmunology 10.1080/2162402X.2016.1186314.
Freund, P., Kerenyi, M.A., Hager, M., Wagner, T., Wingelhofer, B., Pham, H.T., Elabd, M., Han, X., Valent, P., Gouilleux, F., Sexl, V., Kramer, O.H., Groner, B., and Moriggl, R. (2017).
O-GlcNAcylation of STAT5 controls tyrosine phosphorylation and oncogenic transcription in STAT5-dependent malignancies.
Leukemia 10.1038/leu.2017.4
Linke, M., Pham, H.T., Katholnig, K., Schnoller, T., Miller, A., Demel, F., Schutz, B., Rosner, M., Kovacic, B., Sukhbaatar, N., Niederreiter, B., Bluml, S., Kuess, P., Sexl, V., Muller, M., Mikula, M., Weckwerth, W., Haschemi, A., Susani, M., Hengstschlager, M., Gambello, M.J., and Weichhart, T. (2017).
Chronic signaling via the metabolic checkpoint kinase mTORC1 induces macrophage granuloma formation and marks sarcoidosis progression.
Nat Immunol 10.1038/ni.3655
Maurer, B., Farlik, M., and Sexl, V. (2017).
It is a differentiation game: STAT5 in a new role.
Cell Death Differ 10.1038/cdd.2017.71, 953-954
Glasner, A., Levi, A., Enk, J., Isaacson, B., Viukov, S., Orlanski, S., Scope, A., Neuman, T., Enk, C.D., Hanna, J.H., Sexl, V., Jonjic, S., Seliger, B., Zitvogel, L., and Mandelboim, O. (2018).
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