The inhibition of Stat5 by a peptide aptamer ligand specific for the DNA binding domain prevents target gene transactivation and the growth of breast and prostate tumor cells

Pharmaceuticals

Volumn 6, Issue 8, 2013, Pages 960-987

  Weber, Axel ^a   Borghouts, Corina ^b   Brendel, Christian ^c   Moriggl, Richard ^d   Delis, Natalia ^a   Brill, Boris ^a   Vafaizadeh, Vida ^a   Groner, Bernd ^a  

^a INSTITUTE FOR TUMOR BIOLOGY AND EXPERIMENTAL THERAPY   (Germany)

^b Ganymed Pharmaceuticals AG   (Germany)

^c BOSTON CHILDREN S HOSPITAL   (United States)

^d MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

Inhibition of DNA binding; Peptide aptamer (PA); Prostate and breast cancer cell lines; Protein transduction; RNA interference (RNAi); Signal transducer and activator of transcription 5 (Stat5); Yeast two hybrid (Y2H)

Indexed keywords

ANTINEOPLASTIC AGENT; HYBRID PROTEIN; PEPTIDE APTAMER; RECOMBINANT PROTEIN; SCAFFOLD PROTEIN; SHORT HAIRPIN RNA; STAT5 DNA BINDING DOMAIN SPECIFIC PEPTIDE APTAMER; STAT5 PROTEIN; THIOREDOXIN; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; ARTICLE; BACTERIUM; BINDING SITE; BREAST CANCER; CANCER INHIBITION; CARCINOMA CELL; CELL METABOLISM; CONTROLLED STUDY; DNA BINDING; DOWN REGULATION; ENZYME INHIBITION; GENE TARGETING; GENE TRANSFER; GENE VECTOR; HUMAN; HUMAN CELL; PROSTATE CANCER; PROTEIN DNA BINDING; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INTERACTION; RNA INTERFERENCE; TRANSACTIVATION; TUMOR CELL;

EID: 84882616572     PISSN: None     EISSN: 14248247     Source Type: Journal    
DOI: 10.3390/ph6080960     Document Type: Article

References (57)

1. Groner, B.; Hennighausen, L. The versatile regulation of cellular events by jak-stat signaling: From transcriptional control to microtubule dynamics and energy metabolism. Horm. Mol. Biol. Clin. Invest. 2012, 10, 193-200.
2. Levy, D.E.; Darnell, J.E., Jr. Stats: Transcriptional control and biological impact. Nat. Rev. Mol. Cell Biol. 2002, 3, 651-662.
3. Mertens, C.; Darnell, J.E., Jr. Snapshot: Jak-stat signaling. Cell 2007, 131, 612.
4. Reich, N.C.; Liu, L. Tracking stat nuclear traffic. Nat. Rev. Immunol. 2006, 6, 602-612.
5. Mohr, A.; Chatain, N.; Domoszlai, T.; Rinis, N.; Sommerauer, M.; Vogt, M.; Muller-Newen, G. Dynamics and non-canonical aspects of jak/stat signalling. Eur. J. Cell Biol. 2012, 91, 524-532.
6. Lee, J.E.; Yang, Y.M.; Liang, F.X.; Gough, D.J.; Levy, D.E.; Sehgal, P.B. Nongenomic stat5-dependent effects on golgi apparatus and endoplasmic reticulum structure and function. Am. J. Physiol. Cell Physiol. 2012, 302, C804-C820.
7. Wakao, H.; Gouilleux, F.; Groner, B. Mammary gland factor (mgf) is a novel member of the cytokine regulated transcription factor gene family and confers the prolactin response. EMBO J. 1994, 13, 2182-2191.
8. Liu, X.; Robinson, G.W.; Gouilleux, F.; Groner, B.; Hennighausen, L. Cloning and expression of stat5 and an additional homologue (stat5b) involved in prolactin signal transduction in mouse mammary tissue. Proc. Natl. Acad. Sci. USA 1995, 92, 8831-8835.
9. Hennighausen, L.; Robinson, G.W. Interpretation of cytokine signaling through the transcription factors stat5a and stat5b. Genes Dev. 2008, 22, 711-721.
10. Kornfeld, J.W.; Grebien, F.; Kerenyi, M.A.; Friedbichler, K.; Kovacic, B.; Zankl, B.; Hoelbl, A.; Nivarti, H.; Beug, H.; Sexl, V.; et al. The different functions of stat5 and chromatin alteration through stat5 proteins. Front. Biosci. 2008, 13, 6237-6254.
11. Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646-674.
12. Yu, H.; Jove, R. The stats of cancer-New molecular targets come of age. Nat. Rev. Cancer 2004, 4, 97-105.
13. Demaria, M.; Giorgi, C.; Lebiedzinska, M.; Esposito, G.; D'Angeli, L.; Bartoli, A.; Gough, D.J.; Turkson, J.; Levy, D.E.; Watson, C.J.; et al. A stat3-mediated metabolic switch is involved in tumour transformation and stat3 addiction. Aging 2010, 2, 823-842.
14. Lewis, R.S.; Ward, A.C. Stat5 as a diagnostic marker for leukemia. Exp. Rev. Mol. Diagn. 2008, 8, 73-82.
15. Hoelbl, A.; Schuster, C.; Kovacic, B.; Zhu, B.; Wickre, M.; Hoelzl, M.A.; Fajmann, S.; Grebien, F.; Warsch, W.; Stengl, G.; et al. Stat5 is indispensable for the maintenance of bcr/abl-positive leukaemia. EMBO Mol. Med. 2010, 2, 98-110.
16. Heuser, M.; Sly, L.M.; Argiropoulos, B.; Kuchenbauer, F.; Lai, C.; Weng, A.; Leung, M.; Lin, G.; Brookes, C.; Fung, S.; et al. Modeling the functional heterogeneity of leukemia stem cells: Role of stat5 in leukemia stem cell self-renewal. Blood 2009, 114, 3983-3993.
17. Koptyra, M.; Gupta, S.; Talati, P.; Nevalainen, M.T. Signal transducer and activator of transcription 5a/b: Biomarker and therapeutic target in prostate and breast cancer. Int. J. Biochem. Cell Biol. 2011, 43, 1417-1421.
18. Verdine, G.L.; Walensky, L.D. The challenge of drugging undruggable targets in cancer: Lessons learned from targeting bcl-2 family members. Clin. Cancer Res. 2007, 13, 7264-7270.
19. Borghouts, C.; Kunz, C.; Delis, N.; Groner, B. Monomeric recombinant peptide aptamers are required for efficient intracellular uptake and target inhibition. Mol. Cancer Res. 2008, 6, 267-281.
20. Walz, C.; Ahmed, W.; Lazarides, K.; Betancur, M.; Patel, N.; Hennighausen, L.; Zaleskas, V.M.; van Etten, R.A. Essential role for stat5a/b in myeloproliferative neoplasms induced by bcr-abl1 and jak2(v617f) n mice. Blood 2012, 119, 3550-3560.
21. Funakoshi-Tago, M.; Tago, K.; Abe, M.; Sonoda, Y.; Kasahara, T. Stat5 activation is critical for the transformation mediated by myeloproliferative disorder-associated jak2 v617f mutant. J. Biol. Chem. 2010, 285, 5296-5307.
22. Choudhary, C.; Brandts, C.; Schwable, J.; Tickenbrock, L.; Sargin, B.; Ueker, A.; Bohmer, F.D.; Berdel, W.E.; Muller-Tidow, C.; Serve, H. Activation mechanisms of stat5 by oncogenic flt3-itd. Blood 2007, 110, 370-374.
23. Harir, N.; Boudot, C.; Friedbichler, K.; Sonneck, K.; Kondo, R.; Martin-Lanneree, S.; Kenner, L.; Kerenyi, M.; Yahiaoui, S.; Gouilleux-Gruart, V.; et al. Oncogenic kit controls neoplastic mast cell growth through a stat5/pi3-kinase signaling cascade. Blood 2008, 112, 2463-2473.
24. Liao, Z.; Lutz, J.; Nevalainen, M.T. Transcription factor stat5a/b as a therapeutic target protein for prostate cancer. Int. J. Biochem. Cell Biol. 2010, 42, 186-192.
25. Clark, J.; Edwards, S.; Feber, A.; Flohr, P.; John, M.; Giddings, I.; Crossland, S.; Stratton, M.R.; Wooster, R.; Campbell, C.; et al. Genome-wide screening for complete genetic loss in prostate cancer by comparative hybridization onto cdna microarrays. Oncogene 2003, 22, 1247-1252.
26. Van Bokhoven, A.; Varella-Garcia, M.; Korch, C.; Johannes, W.U.; Smith, E.E.; Miller, H.L.; Nordeen, S.K.; Miller, G.J.; Lucia, M.S. Molecular characterization of human prostate carcinoma cell lines. Prostate 2003, 57, 205-225.
27. Dagvadorj, A.; Collins, S.; Jomain, J.B.; Abdulghani, J.; Karras, J.; Zellweger, T.; Li, H.; Nurmi, M.; Alanen, K.; Mirtti, T.; et al. Autocrine prolactin promotes prostate cancer cell growth via janus kinase-2-signal transducer and activator of transcription-5a/b signaling pathway. Endocrinology 2007, 148, 3089-3101.
28. Evans, M.K.; Yu, C.R.; Lohani, A.; Mahdi, R.M.; Liu, X.; Trzeciak, A.R.; Egwuagu, C.E. Expression of socs1 and socs3 genes is differentially regulated in breast cancer cells in response to proinflammatory cytokine and growth factor signals. Oncogene 2007, 26, 1941-1948.
29. Olayioye, M.A.; Beuvink, I.; Horsch, K.; Daly, J.M.; Hynes, N.E. Erbb receptor-induced activation of stat transcription factors is mediated by src tyrosine kinases. J. Biol. Chem. 1999, 274, 17209-17218.
30. Tan, S.H.; Dagvadorj, A.; Shen, F.; Gu, L.; Liao, Z.; Abdulghani, J.; Zhang, Y.; Gelmann, E.P.; Zellweger, T.; Culig, Z.; et al. Transcription factor stat5 synergizes with androgen receptor in prostate cancer cells. Cancer Res. 2008, 68, 236-248.
31. Dagvadorj, A.; Kirken, R.A.; Leiby, B.; Karras, J.; Nevalainen, M.T. Transcription factor signal transducer and activator of transcription 5 promotes growth of human prostate cancer cells in vivo. Clinical Cancer Res. 2008, 14, 1317-1324.
32. Thomas, C.; Zoubeidi, A.; Kuruma, H.; Fazli, L.; Lamoureux, F.; Beraldi, E.; Monia, B.P.; MacLeod, A.R.; Thuroff, J.W.; Gleave, M.E. Transcription factor stat5 knockdown enhances androgen receptor degradation and delays castration-resistant prostate cancer progression in vivo. Mol. Cancer Ther. 2011, 10, 347-359.
33. Hassel, J.C.; Winnemoller, D.; Schartl, M.; Wellbrock, C. Stat5 contributes to antiapoptosis in melanoma. Melanoma Res. 2008, 18, 378-385.
34. Mirmohammadsadegh, A.; Hassan, M.; Bardenheuer, W.; Marini, A.; Gustrau, A.; Nambiar, S.; Tannapfel, A.; Bojar, H.; Ruzicka, T.; Hengge, U.R. Stat5 phosphorylation in malignant melanoma is important for survival and is mediated through src and jak1 kinases. J. Invest. Dermatol. 2006, 126, 2272-2280.
35. Walker, S.R.; Nelson, E.A.; Zou, L.; Chaudhury, M.; Signoretti, S.; Richardson, A.; Frank, D.A. Reciprocal effects of stat5 and stat3 in breast cancer. Mol. Cancer Res. 2009, 7, 966-976.
36. Gutzman, J.H.; Rugowski, D.E.; Nikolai, S.E.; Schuler, L.A. Stat5 activation inhibits prolactin-induced ap-1 activity: Distinct prolactin-initiated signals in tumorigenesis dependent on cell context. Oncogene 2007, 26, 6341-6348.
37. Sultan, A.S.; Xie, J.; LeBaron, M.J.; Ealley, E.L.; Nevalainen, M.T.; Rui, H. Stat5 promotes homotypic adhesion and inhibits invasive characteristics of human breast cancer cells. Oncogene 2005, 24, 746-760.
38. Grimm, D.; Streetz, K.L.; Jopling, C.L.; Storm, T.A.; Pandey, K.; Davis, C.R.; Marion, P.; Salazar, F.; Kay, M.A. Fatality in mice due to oversaturation of cellular microrna/short hairpin rna pathways. Nature 2006, 441, 537-541.
39. Yan, S.J.; Lim, S.J.; Shi, S.; Dutta, P.; Li, W.X., Unphosphorylated stat and heterochromatin protect genome stability. FASEB J. 2011, 25, 232-241.
40. Li, W.X. Canonical and non-canonical jak-stat signaling. Trends Cell Biol. 2008, 18, 545-551.
41. Chueh, F.Y.; Leong, K.F.; Yu, C.L. Mitochondrial translocation of signal transducer and activator of transcription 5 (stat5) in leukemic t cells and cytokine-stimulated cells. Biochem. Biophys. Res. Commun. 2010, 402, 778-783.
42. Gilbert, S.; Zhang, R.; Denson, L.; Moriggl, R.; Steinbrecher, K.; Shroyer, N.; Lin, J.; Han, X. Enterocyte stat5 promotes mucosal wound healing via suppression of myosin light chain kinase-mediated loss of barrier function and inflammation. EMBO Mol. Med. 2012, 4, 109-124.
43. Bickle, M.B.; Dusserre, E.; Moncorge, O.; Bottin, H.; Colas, P. Selection and characterization of large collections of peptide aptamers through optimized yeast two-hybrid procedures. Nat. protoc. 2006, 1, 1066-1091.
44. Colas, P. The eleven-year switch of peptide aptamers. J. Biol. 2008, 7, 2.
45. Hamdi, A.; Colas, P. Yeast two-hybrid methods and their applications in drug discovery. Trends Pharmacol. Sci. 2012, 33, 109-118.
46. Borghouts, C.; Kunz, C.; Groner, B. Peptide aptamer libraries. Comb. Chem. High Throughput Screen. 2008, 11, 135-145.
47. Becker, S.; Groner, B.; Muller, C.W. Three-dimensional structure of the stat3beta homodimer bound to DNA. Nature 1998, 394, 145-151.
48. Borghouts, C.; Delis, N.; Brill, B.; Weiss, A.; Mack, L.; Lucks, P.; Groner, B. A membrane penetrating aptamer inhibits stat3 function and suppresses the growth of stat3 addicted tumor cells. JAK-STAT 2012, 1, 44-54.
49. Melen, K.; Fagerlund, R.; Franke, J.; Kohler, M.; Kinnunen, L.; Julkunen, I. Importin alpha nuclear localization signal binding sites for stat1, stat2, and influenza a virus nucleoprotein. J. Biol. Chem. 2003, 278, 28193-28200.
50. Groner, B. Transcription factor regulation in mammary epithelial cells. Domest. Anim. Endocrinol. 2002, 23, 25-32.
51. Engblom, D.; Kornfeld, J.W.; Schwake, L.; Tronche, F.; Reimann, A.; Beug, H.; Hennighausen, L.; Moriggl, R.; Schutz, G. Direct glucocorticoid receptor-stat5 interaction in hepatocytes controls body size and maturation-related gene expression. Genes Dev. 2007, 21, 1157-1162.
52. Demaison, C.; Parsley, K.; Brouns, G.; Scherr, M.; Battmer, K.; Kinnon, C.; Grez, M.; Thrasher, A.J. High-level transduction and gene expression in hematopoietic repopulating cells using a human immunodeficiency [correction of imunodeficiency] virus type 1-based lentiviral vector containing an internal spleen focus forming virus promoter. Human Gene Ther. 2002, 13, 803-813.
53. Butz, K.; Denk, C.; Ullmann, A.; Scheffner, M.; Hoppe-Seyler, F. Induction of apoptosis in human papillomaviruspositive cancer cells by peptide aptamers targeting the viral e6 oncoprotein. Proc. Natl. Acad. Sci. USA 2000, 97, 6693-6697.
54. Baines, I.C.; Colas, P. Peptide aptamers as guides for small-molecule drug discovery. Drug Discov. Today 2006, 11, 334-341.
55. Wathes, R.; Moule, S.; Milojkovic, D. Progressive multifocal leukoencephalopathy associated with ruxolitinib. N. Engl. J. Med. 2013, 369, 197-198.
56. Groner, B.; Weber, A.; Mack, L. Increasing the range of drug targets: Interacting peptides provide leads for the development of oncoprotein inhibitors. Bioengineered 2012, 3, 320-325.
57. Bardou, C.; Borie, C.; Bickle, M.; Rudkin, B.B.; Colas, P. Peptide aptamers for small molecule drug discovery. Methods Mol. Biol. 2009, 535, 373-388.