Nuclear receptor NR4A1 promotes breast cancer invasion and metastasis by activating TGF-β signalling

Nature Communications

Volumn 5, Issue , 2014, Pages

  Zhou, FangFang ^a,b   Drabsch, Yvette ^b   Dekker, Tim J A ^b   De Vinuesa, Amaya Garcia ^b   Li, Yihao ^b   Hawinkels, Lukas J A C ^b   Sheppard, Kelly Ann ^c   Goumans, Marie José ^b   Luwor, Rodney B ^d   De Vries, Carlie J ^e   Mesker, Wilma E ^b   Tollenaar, Rob A E M ^b   Devilee, Peter ^b   Lu, Chris X ^c   Zhu, Hongjian ^d   Zhang, Long ^a   Ten Dijke, Peter ^a,b  

^a ZHEJIANG UNIVERSITY   (China)

^b LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^c NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^d UNIVERSITY OF MELBOURNE   (Australia)

^e UNIVERSITY OF AMSTERDAM   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ARKADIA PROTEIN; AXIN; AXIN2 PROTEIN; BINDING PROTEIN; COMPLEMENTARY DNA; CYTOKINE; NUCLEAR RECEPTOR NUR77; RING FINGER PROTEIN; RING FINGER PROTEIN 12; SMAD PROTEIN; SMAD2 PROTEIN; SMAD7 PROTEIN; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; SMAD3 PROTEIN; SMAD3 PROTEIN, MOUSE; SMAD4 PROTEIN; SMAD4 PROTEIN, MOUSE;

CANCER; CELLS AND CELL COMPONENTS; GENE EXPRESSION; GENOME; PROTEIN;

ANIMAL CELL; ANIMAL MODEL; ARTICLE; BREAST CANCER; BREAST CANCER CELL LINE; CANCER CELL; CANCER PATIENT; CANCER PROGNOSIS; CELL INVASION; CELL MIGRATION; CONTROLLED STUDY; DISTANT METASTASIS; EMBRYO; EPITHELIAL MESENCHYMAL TRANSITION; FEMALE; GENETIC ASSOCIATION; GROWTH INHIBITION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; MALE; METASTASIS; MOUSE; NONHUMAN; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; TUMOR XENOGRAFT; ANIMAL; CELL CULTURE; CHROMATIN IMMUNOPRECIPITATION; EXPERIMENTAL MAMMARY NEOPLASM; GENETICS; IMMUNOHISTOCHEMISTRY; KNOCKOUT MOUSE; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; UBIQUITINATION; ZEBRA FISH;

ANIMALS; CELLS, CULTURED; CHROMATIN IMMUNOPRECIPITATION; FEMALE; IMMUNOHISTOCHEMISTRY; MAMMARY NEOPLASMS, ANIMAL; MICE; MICE, KNOCKOUT; NEOPLASM METASTASIS; NUCLEAR RECEPTOR SUBFAMILY 4, GROUP A, MEMBER 1; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SMAD3 PROTEIN; SMAD4 PROTEIN; TRANSFORMING GROWTH FACTOR BETA; UBIQUITINATION; ZEBRAFISH;

EID: 84900434811     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms4388     Document Type: Article

References (45)

1. Massagué, J. TGFβ in Cancer. Cell 134, 215-230 (2008).
2. Moustakas, A. & Heldin, C. H. The regulation of TGFβ signal transduction. Development 136, 3699-3714 (2009).
3. Derynck, R. & Akhurst, R. J. Differentiation plasticity regulated by TGF-β family proteins in development and disease. Nat. Cell Biol. 9, 1000-1004 (2007).
4. Schmierer, B. & Hill, C. S. TGFβ-SMAD signal transduction: molecular specificity and functional flexibility. Nat. Rev. Mol. Cell Biol. 8, 970-982 (2007).
5. Kang, J. S., Liu, C. & Derynck, R. New regulatory mechanisms of TGF-β receptor function. Trends Cell Biol. 19, 385-394 (2009).
6. Kavsak, P. et al. Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGFβ receptor for degradation. Mol. Cell. 6, 1365-1375 (2000).
7. Ebisawa, T. et al. Smurf1 interacts with transforming growth factor-β type I receptor through Smad7 and induces receptor degradation. J. Biol. Chem. 276, 12477-12480 (2001).
8. Koinuma, D. et al. Arkadia amplifies TGF-β superfamily signalling through degradation of Smad7. EMBO J. 22, 6458-6470 (2003).
9. Zhang, L. et al. RNF12 controls embryonic stem cell fate and morphogenesis in zebrafish embryos by targeting Smad7 for degradation. Mol. Cell 46, 650-661 (2012).
10. Meulmeester, E. & Ten Dijke, P. The dynamic roles of TGF-β in cancer. J. Pathol. 223, 205-218 (2011).
11. Winoto, A. & Littman, D. R. Nuclear hormone receptors in T lymphocytes. Cell 109(Suppl), S57-S66 (2002).
12. Liu, Z. G., Smith, S. W., McLaughlin, K. A., Schwartz, L. M. & Osborne, B. A. Apoptotic signals delivered through the T-cell receptor of a T-cell hybrid require the immediate-early gene nur77. Nature 367, 281-284 (1994).
13. Woronicz, J. D., Calnan, B., Ngo, V. & Winoto, A. Requirement for the orphan steroid receptor Nur77 in apoptosis of T-cell hybridomas. Nature 367, 277-281 (1994).
14. Lin, B. et al. Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3. Cell 116, 527-540 (2004).
15. Mullican, S. E. et al. Abrogation of nuclear receptors Nr4a3 and Nr4a1 leads to development of acute myeloid leukemia. Nat. Med. 13, 730-735 (2007).
16. Wu, H. et al. Regulation of Nur77 expression by β-catenin and its mitogenic effect in colon cancer cells. FASEB J. 25, 192-205 (2011).
17. Lee, S. O. et al. Inactivation of the orphan nuclear receptor TR3/Nur77 inhibits pancreatic cancer cell and tumor growth. Cancer Res. 70, 6824-6836 (2010).
18. Strausberg, R. L., Feingold, E. A., Klausner, R. D. & Collins, F. S. The mammalian gene collection. Science 286, 455-457 (1999).
19. Di Guglielmo, G. M., Le Roy, C., Goodfellow, A. F. & Wrana, J. L. Distinct endocytic pathways regulate TGF-β receptor signalling and turnover. Nat. Cell Biol. 5, 410-421 (2003).
20. Niederlander, C., Walsh, J. J., Episkopou, V. & Jones, C. M. Arkadia enhances nodal-related signalling to induce mesendoderm. Nature 410, 830-834 (2001).
21. Episkopou, V. et al. Induction of the mammalian node requires Arkadia function in the extraembryonic lineages. Nature 410, 825-830 (2001).
22. Liu, W. et al. Axin is a scaffold protein in TGF-β signaling that promotes degradation of Smad7 by Arkadia. EMBO J. 25, 1646-1658 (2006).
23. Davis, I. J., Hazel, T. G. & Lau, L. F. Transcriptional activation by Nur77, a growth factor-inducible member of the steroid hormone receptor superfamily. Mol. Endocrinol. 5, 854-859 (1991).
24. Pei, L. et al. NR4A orphan nuclear receptors are transcriptional regulators of hepatic glucose metabolism. Nat. Med. 12, 1048-1055 (2006).
25. Pei, L., Castrillo, A., Chen, M., Hoffmann, A. & Tontonoz, P. Induction of NR4A orphan nuclear receptor expression in macrophages in response to inflammatory stimuli. J. Biol. Chem. 280, 29256-29262 (2005).
26. Ikushima, H. & Miyazono, K. TGFβ signalling: a complex web in cancer progression. Nat. Rev. Cancer 10, 415-424 (2010).
27. Xu, J., Lamouille, S. & Derynck, R. TGF-β-induced epithelial to mesenchymal transition. Cell. Res 19, 156-172 (2009).
28. Thiery, J. P., Acloque, H., Huang, R. Y. & Nieto, M. A. Epithelial-mesenchymal transitions in development and disease. Cell 139, 871-890 (2009).
29. Kang, Y. et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3, 537-549 (2003).
30. Bandyopadhyay, A. et al. Inhibition of pulmonary and skeletal metastasis by a transforming growth factor-β type I receptor kinase inhibitor. Cancer Res. 66, 6714-6721 (2006).
31. Zhang, L. et al. USP4 is regulated by AKT phosphorylation and directly deubiquitylates TGF-β type I receptor. Nat. Cell Biol. 14, 717-726 (2012).
32. Wu, Z. Q. et al. Canonical Wnt suppressor, Axin2, promotes colon carcinoma oncogenic activity. Proc. Natl Acad. Sci. USA 109, 11312-11317 (2012).
33. Guo, X. et al. Axin and GSK3- control Smad3 protein stability and modulate TGF-β signaling. Genes Dev. 22, 106-120 (2008).
34. Coussens, L. M. & Werb, Z. Inflammation and cancer. Nature 420, 860-867 (2002).
35. Eckhardt, B. L., Francis, P. A., Parker, B. S. & Anderson, R. L. Strategies for the discovery and development of therapies for metastatic breast cancer. Nat. Rev. Drug Discov. 11, 479-497 (2012).
36. Fuxe, J. & Karlsson, M. C. I. TGF-β-induced epithelial-mesenchymal transition: A link between cancer and inflammation. Semin. Cancer Biol. 22, 455-461 (2012).
37. Mantovani, A., Allavena, P., Sica, A. & Balkwill, F. Cancer-related inflammation. Nature 454, 436-444 (2008).
38. Ulloa, L., Doody, J. & Massagué, J. Inhibition of transforming growth factor-β/SMAD signalling by the interferon-gamma/STAT pathway. Nature 397, 710-713 (1999).
39. Ikeda, H., Old, L. J. & Schreiber, R. D. The roles of IFN gamma in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev. 13, 95-109 (2002).
40. Lee, S. L. et al. Unimpaired thymic and peripheral T cell death in mice lacking the nuclear receptor NGFI-B (Nur77). Science 269, 532-535 (1995).
41. Pols, T. W. et al. Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity. Biochem. Biophys. Res. Commun. 366, 910-916 (2008).
42. Zhang, L. et al. Zebrafish Dpr2 inhibits mesoderm induction by promoting degradation of nodal receptors. Science 306, 114-117 (2004).
43. Zhou, F., Zhang, L., van Laar, T., van Dam, H. & Ten Dijke, P. GSK3β inactivation induces apoptosis of leukemia cells by repressing the function of c-Myb. Mol. Biol. Cell 22, 3533-3540 (2011).
44. He, S. et al. Neutrophil-mediated experimental metastasis is enhanced by VEGFR inhibition in a zebrafish xenograft model. J. Pathol. 227, 431-445 (2012).
45. Arguello, F., Baggs, R. B. & Frantz, C. N. A murine model of experimental metastasis to bone and bone marrow. Cancer Res. 48, 6876-6881 (1988).