Monoclonal antibodies specific for Stat3β reveal its contribution to constitutive Stat3 phosphorylation in breast cancer

Cancers

Volumn 6, Issue 4, 2014, Pages 2012-2034

  Bharadwaj, Uddalak ^a   Kasembeli, Moses M ^a   Eckols, T Kris ^a   Kolosov, Mikhail ^a   Lang, Paul ^a   Christensen, Kurt ^a   Edwards, Dean P ^a   Tweardy, David J ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

Alternative RNA splicing; Breast cancer; CT7; Isoform; Monoclonal; Oncogenesis; Phosphorylation; Regulation; Stat3 beta; Stat3

Indexed keywords

MONOCLONAL ANTIBODY; STAT3 PROTEIN; STAT3ALPHA PROTEIN; STAT3BETA PROTEIN; UNCLASSIFIED DRUG;

ALTERNATIVE RNA SPLICING; ANIMAL CELL; ANTIBODY SPECIFICITY; ANTIGEN RECOGNITION; ARTICLE; BREAST CANCER; BREAST CARCINOGENESIS; CANCER CELL; CARBOXY TERMINAL SEQUENCE; CELL LEVEL; CONTROLLED STUDY; EPITOPE MAPPING; GENE OVEREXPRESSION; HUMAN; HUMAN CELL; IMMUNOBLOTTING; MOUSE; NONHUMAN; PROTEIN CROSS LINKING; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION;

EID: 84907665167     PISSN: None     EISSN: 20726694     Source Type: Journal    
DOI: 10.3390/cancers6042012     Document Type: Article

References (56)

1. Darnell, J.E. Jr.; Kerr I.M.; Stark G.R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 1994, 264, 1415–1421.
2. Bode, J.G.; Albrecht U.; Haussinger D.; Heinrich P.C.; Schaper F. Hepatic acute phase proteins—Regulation by IL-6- and IL-1-type cytokines involving STAT3 and its crosstalk with NF-kappaB-dependent signaling. Eur. J. Cell Biol. 2012, 91, 496–505.
3. He, G.; Karin M. NF-kappaB and STAT3-key players in liver inflammation and cancer. Cell Res. 2011, 21, 159–168.
4. Li, N.; Grivennikov S.I.; Karin M. The unholy trinity: inflammation, cytokines, and STAT3 shape the cancer microenvironment. Cancer Cell 2011, 19, 429–431.
5. Bharadwaj, U.; Eckols T.K.; Kolosov M.; Kasembeli M.M.; Adam A.; Torres D.; Zhang X.; Dobrolecki L.E.; Wei W.; Lewis, M.T. et al. Drug-repositioning screening identified piperlongumine as a direct STAT3 inhibitor with potent activity against breast cancer. Oncogene 2014, doi:10.1038/onc.2014.72.
6. Bharadwaj, U.; Li M.; Chen C.; Yao, Q. Mesothelin-induced pancreatic cancer cell proliferation involves alteration of cyclin E via activation of signal transducer and activator of transcription protein 3. Mol. Cancer Res. 2008, 6, 1755–1765.
7. Bharadwaj, U.; Li M.; Zhang R.; Chen C.; Yao Q. Elevated interleukin-6 and G-CSF in human pancreatic cancer cell conditioned medium suppress dendritic cell differentiation and activation. Cancer Res. 2007, 67, 5479–5488.
8. Bharadwaj, U.; Marin-Muller C.; Li M.; Chen C.; Yao Q. Mesothelin overexpression promotes autocrine IL-6/sIL-6R trans-signaling to stimulate pancreatic cancer cell proliferation. Carcinogenesis 2011, 32, 1013–1024.
9. Rossa, C. Jr.; Sommer G.; Spolidorio L.C.; Rosenzweig S.A.; Watson D.K.; Kirkwood, K.L. Loss of expression and function of SOCS3 is an early event in HNSCC: Altered subcellular localization as a possible mechanism involved in proliferation, migration and invasion. PLoS One 2012, 7, e45197.
10. Ishida, F.; Matsuda K.; Sekiguchi N.; Makishima H.; Taira C.; Momose K.; Nishina S.; Senoo N.; Sakai H.; Ito, T. et al. STAT3 gene mutations and their association with pure red cell aplasia in large granular lymphocyte leukemia. Cancer Sci. 2014, 105, 342–346.
11. Munoz, J.; Dhillon N.; Janku F.; Watowich S.S.; Hong D.S. STAT3 Inhibitors: Finding a home in lymphoma and leukemia. Oncologist 2014, 19, 536–544.
12. Shao, H.; Quintero A.J.; Tweardy D.J. Identification and characterization of cis elements in the STAT3 gene regulating STAT3 alpha and STAT3 beta messenger RNA splicing. Blood 2001, 98, 3853–3856.
13. Kato, T.; Sakamoto E.; Kutsuna H.; Kimura-Eto A.; Hato F.; Kitagawa S. Proteolytic conversion of STAT3alpha to STAT3gamma in human neutrophils: Role of granule-derived serine proteases. J. Biol. Chem. 2004, 279, 31076–31080.
14. Biethahn, S.; Alves F.; Wilde S.; Hiddemann W.; Spiekermann K. Expression of granulocyte colony-stimulating factor- and granulocyte-macrophage colony-stimulating factor-associated signal transduction proteins of the JAK/STAT pathway in normal granulopoiesis and in blast cells of acute myelogenous leukemia. Exp. Hematol. 1999, 27, 885–894.
15. Chakraborty, A.; White S.M.; Schaefer T.S.; Ball E.D.; Dyer K.F.; Tweardy D.J. Granulocyte colony-stimulating factor activation of Stat3 alpha and Stat3 beta in immature normal and leukemic human myeloid cells. Blood 1996, 88, 2442–2449.
16. Caldenhoven, E.; van Dijk T.B.; Solari R.; Armstrong J.; Raaijmakers J.A.; Lammers J.W.; Koenderman L.; de Groot R.P. STAT3beta, a splice variant of transcription factor STAT3, is a dominant negative regulator of transcription. J. Biol. Chem. 1996, 271, 13221–13227.
17. Kunz, D.; Zimmermann R.; Heisig M.; Heinrich P.C. Identification of the promoter sequences involved in the interleukin-6 dependent expression of the rat alpha 2-macroglobulin gene. Nucleic Acids Res. 1989, 17, 1121–1138.
18. Kushner, I. The phenomenon of the acute phase response. Ann. N. Y. Acad. Sci. 1982, 389, 39–48.
19. Schaefer, T.S.; Sanders L.K.; Nathans, D. Cooperative transcriptional activity of Jun and Stat3beta, a short form of Stat3. Proc. Natl. Acad. Sci. USA 1995, 92, 9097–9101.
20. Schaefer, T.S.; Sanders L.K.; Park O.K.; Nathans D. Functional differences between Stat3alpha and Stat3beta. Mol. Cell. Biol. 1997, 17, 5307–5316.
21. Ivanov, V.N.; Bhoumik A.; Krasilnikov M.; Raz R.; Owen-Schaub L.B.; Levy D.; Horvath C.M.; Ronai Z. Cooperation between STAT3 and c-jun suppresses Fas transcription. Mol. Cell 2001, 7, 517–528.
22. Yoo, J.Y.; Huso D.L.; Nathans D.; Desiderio S. Specific ablation of Stat3beta distorts the pattern of Stat3-responsive gene expression and impairs recovery from endotoxic shock. Cell 2002, 108, 331–344.
23. Maritano, D.; Sugrue M.L.; Tininini S.; Dewilde S.; Strobl B.; Fu X.; Murray-Tait V.; Chiarle R.; Poli V. The STAT3 isoforms alpha and beta have unique and specific functions. Nat. Immunol. 2004, 5, 401–409.
24. Dewilde, S.; Vercelli A.; Chiarle R.; Poli V. Of alphas and betas: Distinct and overlapping functions of STAT3 isoforms. Front. Biosci. 2008, 13, 6501–6514.
25. Hevehan, D.L.; Miller W.M.; Papoutsakis E.T. Differential expression and phosphorylation of distinct STAT3 proteins during granulocytic differentiation. Blood 2002, 99, 1627–1637.
26. Minami, M.; Inoue M.; Wei S.; Takeda K.; Matsumoto M.; Kishimoto T.; Akira S. STAT3 activation is a critical step in gp130-mediated terminal differentiation and growth arrest of a myeloid cell line. Proc. Natl. Acad. Sci. USA 1996, 93, 3963–3966.
27. Huang, Y.; Qiu J.; Dong S.; Redell M.S.; Poli V.; Mancini M.A.; Tweardy D.J. Stat3 isoforms, alpha and beta, demonstrate distinct intracellular dynamics with prolonged nuclear retention of Stat3beta mapping to its unique C-terminal end. J. Biol. Chem. 2007, 282, 34958–34967.
28. Ng, I.H.; Ng D.C.; Jans D.A.; Bogoyevitch M.A. Selective STAT3-alpha or -beta expression reveals spliceform-specific phosphorylation kinetics, nuclear retention and distinct gene expression outcomes. Biochem. J. 2012, 447, 125–136.
29. Sasse, J.; Hemmann U.; Schwartz C.; Schniertshauer U.; Heesel B.; Landgraf C.; Schneider-Mergener J.; Heinrich P.C.; Horn, F. Mutational analysis of acute-phase response factor/Stat3 activation and dimerization. Mol. Cell. Biol. 1997, 17, 4677–4686.
30. Foley, H.A.; Ofori-Acquah S.F.; Yoshimura A.; Critz S.; Baliga B.S.; Pace B.S. Stat3 beta inhibits gamma-globin gene expression in erythroid cells. J. Biol. Chem. 2002, 277, 16211–16219.
31. Zammarchi, F.; de Stanchina E.; Bournazou E.; Supakorndej T.; Martires K.; Riedel E.; Corben A.D.; Bromberg J.F.; Cartegni L. Antitumorigenic potential of STAT3 alternative splicing modulation. Proc. Natl. Acad. Sci. USA 2011, 108, 17779–17784.
32. Christensen, K. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. Unpublished data, 2013.
33. Kasembeli, M.M. Section of Infectious Disease, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. Unpublished data, 2014.
34. Xu, X.; Kasembeli M.M.; Jiang X.; Tweardy B.J.; Tweardy D.J. Chemical probes that competitively and selectively inhibit Stat3 activation. PLoS One 2009, 4, e4783.
35. Alten, J.A.; Moran A.; Tsimelzon A.I.; Mastrangelo M.A.; Hilsenbeck S.G.; Poli V.; Tweardy D.J. Prevention of hypovolemic circulatory collapse by IL-6 activated Stat3. PLoS One 2008, 3, e1605.
36. Moran, A.; Arikan A.A.; Mastrangelo M.A.; Wu Y.; Yu B.; Poli V.; Tweardy, D.J. Prevention of trauma and hemorrhagic shock-mediated liver apoptosis by activation of stat3alpha. Int. J. Clin. Exp. Med. 2008, 1, 213–247.
37. Moran, A.; Thacker S.A.; Arikan A.A.; Mastrangelo M.A.; Wu Y.; Yu B.; Tweardy D.J. IL-6-mediated activation of Stat3alpha prevents trauma/hemorrhagic shock-induced liver inflammation. PLoS One 2011, 6, e21449.
38. Moran, A.; Tsimelzon A.I.; Mastrangelo M.A.; Wu Y.; Yu B.; Hilsenbeck S.G.; Poli V.; Tweardy D.J. Prevention of trauma/hemorrhagic shock-induced lung apoptosis by IL-6-mediated activation of Stat3. Clin. Transl. Sci. 2009, 2, 41–49.
39. Scholz, A.; Heinze S.; Detjen K.M.; Peters M.; Welzel M.; Hauff P.; Schirner M.; Wiedenmann B.; Rosewicz S. Activated signal transducer and activator of transcription 3 (STAT3) supports the malignant phenotype of human pancreatic cancer. Gastroenterology 2003, 125, 891–905.
40. Turkson, J.; Bowman T.; Garcia R.; Caldenhoven E.; de Groot R.P.; Jove R. Stat3 activation by Src induces specific gene regulation and is required for cell transformation. Mol. Cell. Biol. 1998, 18, 2545–2552.
41. Discovery Services. Available online: http://dtp.nci.nih.gov/docs/misc/common_files/mda-mb-435-update.html (accessed on 22 August 2014).
42. Burke, W.M.; Jin X.; Lin H.J.; Huang M.; Liu R.; Reynolds R.K.; Lin J. Inhibition of constitutively active Stat3 suppresses growth of human ovarian and breast cancer cells. Oncogene 2001, 20, 7925–7934.
43. Ni, Z.; Lou W.; Leman E.S.; Gao A.C. Inhibition of constitutively activated Stat3 signaling pathway suppresses growth of prostate cancer cells. Cancer Res. 2000, 60, 1225–1228.
44. Niu, G.; Heller R.; Catlett-Falcone R.; Coppola D.; Jaroszeski M.; Dalton W.; Jove R.; Yu H. Gene therapy with dominant-negative Stat3 suppresses growth of the murine melanoma B16 tumor in vivo. Cancer Res. 1999, 59, 5059–5063.
45. Benekli, M.; Xia Z.; Donohue K.A.; Ford L.A.; Pixley L.A.; Baer M.R.; Baumann H.; Wetzler M. Constitutive activity of signal transducer and activator of transcription 3 protein in acute myeloid leukemia blasts is associated with short disease-free survival. Blood 2002, 99, 252–257.
46. Xia, Z.; Sait S.N.; Baer M.R.; Barcos M.; Donohue K.A.; Lawrence D.; Ford L.A.; Block A.M.; Baumann H.; Wetzler, M. et al. Truncated STAT proteins are prevalent at relapse of acute myeloid leukemia. Leuk. Res. 2001, 25, 473–482.
47. Ramadoss, P.; Unger-Smith N.E.; Lam F.S.; Hollenberg A.N. STAT3 targets the regulatory regions of gluconeogenic genes in vivo. Mol. Endocrinol. 2009, 23, 827–837.
48. Marotta, L.L.; Almendro V.; Marusyk A.; Shipitsin M.; Schemme J.; Walker S.R.; Bloushtain-Qimron N.; Kim J.J.; Choudhury S.A.; Maruyama, R. et al. The JAK2/STAT3 signaling pathway is required for growth of CD44CD24 stem cell-like breast cancer cells in human tumors. J. Clin. Investig. 2011, 121, 2723–2735.
49. Bonnal, S.; Vigevani L.; Valcarcel J. The spliceosome as a target of novel antitumour drugs. Nat. Rev. Drug Discov. 2012, 11, 847–859.
50. Elsarraj, H.S.; Hong Y.; Valdez K.; Carletti M.; Salah S.M.; Raimo M.; Taverna D.; Prochasson P.; Bharadwaj U.; Tweardy, D.J. et al. A novel role of microRNA146b in promoting mammary alveolar progenitor cell maintenance. J. Cell Sci. 2013, 126, 2446–2458.
51. Xia, H.; Qi Y.; Ng S.S.; Chen X.; Li D.; Chen S.; Ge R.; Jiang S.; Li G.; Chen, Y. et al. microRNA-146b inhibits glioma cell migration and invasion by targeting MMPs. Brain Res. 2009, 1269, 158–165.
52. Walker, S.R.; Xiang M.; Frank D.A. STAT3 Activity and Function in Cancer: Modulation by STAT5 and miR-146b. Cancers (Basel) 2014, 6, 958–968.
53. Xiang, M.; Birkbak N.J.; Vafaizadeh V.; Walker S.R.; Yeh J.E.; Liu S.; Kroll Y.; Boldin M.; Taganov K.; Groner, B. et al. STAT3 induction of miR-146b forms a feedback loop to inhibit the NF-kappaB to IL-6 signaling axis and STAT3-driven cancer phenotypes. Sci. Signal. 2014, doi:10.1126/scisignal.2004497.
54. Costa-Pereira, A.P.; Tininini S.; Strobl B.; Alonzi T.; Schlaak J.F.; Is’harc H.; Gesualdo I.; Newman S.J.; Kerr I.M.; Poli, V. et al. Mutational switch of an IL-6 response to an interferon-gamma-like response. Proc. Natl. Acad. Sci. USA 2002, 99, 8043–8047.
55. Shao, H.; Cheng H.Y.; Cook R.G.; Tweardy D.J. Identification and characterization of signal transducer and activator of transcription 3 recruitment sites within the epidermal growth factor receptor. Cancer Res. 2003, 63, 3923–3930.
56. ImageJ: Image Processing and Analysis in Java. Available online: http://imagej.nih.gov/ij/ (accessed on 22 August 2014).