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Cooperation between Myc and YY1 provides novel silencing transcriptional targets of α3β1-integrin in tumour cells

Oncogene volume 26, pages 382–394 (2007)Cite this article

Abstract

We show that human osteosarcoma cells (Saos-2) have downregulation of α3β1-integrin compared to normal bone cells; this was further described in human osteosarcomas and in a primary murine sarcoma. The α3 gene was silenced in Saos-2 cells causing a low expression of α3β1-integrin and reduction in collagen attachment with increasing migratory capacity. Chromatin immunoprecipitation assay performed on α3 promoter established that Myc and Yin Yang protein (YY1) cooperate in tandem to downregulate the α3 gene. This silencing mechanism involves the binding of Myc and YY1 to DNA and formation of complexes among Myc/Max, YY1, CREB-binding protein and deacetylation activity. The promoter containing deletions of E-boxes or YY1 cassettes failed to downregulate the transcription of a reporter gene as well as the inhibition of deacetylation activity. Overexpression of both Myc and YY1 was necessary to determine the α3-integrin promoter downregulation in normal osteoblasts. This downregulation of α3β1-integrin can contribute to the acquisition of a more aggressive phenotype. YY1 regulated negatively the Myc activity through a direct interaction with the Myc/Max and deacetylase complexes. This represents a novel silencing mechanism with broad implications in the transcription machinery of tumours.

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References

  • Arndt CA, Crist WM . (1999). N Engl J Med 341: 342–352.

  • Brockbank EC, Bridges J, Marshall CJ, Sahai E . (2005). Br J Cancer 92: 102–112.

  • Dang CV, Lewis BC . (1997). J Biomed Sci 4: 269–278.

  • Davie JR, Chadee DN . (1998). J Cell Biochem Suppl 30–31: 203–213.

  • de Nigris F, Youssef T, Ciafre S, Franconi F, Anania V, Condorelli G et al. (2000). Circulation 102: 2111–2117.

  • de Nigris F, Mega T, Berger N, Barone MV, Santoro M, Viglietto G et al. (2001). Cancer Res 61: 2267–2275.

  • de Nigris F, Cerutti J, Morelli C, Califano D, Chiariotti L, Viglietto G et al. (2002). Br J Cancer 87: 1479.

  • de Nigris F, Sica V, Herrmann J, Condorelli G, Chade AR, Tajana G et al. (2003). Cell Cycle 2: 325–328.

  • Donohoe ME, Zhang X, McGinnis L, Biggers J, Li E, Shi Y . (1999). Mol Cell Biol 19: 7237–7244.

  • Flanagan JR, Becker KG, Ennist DL, Gleason SL, Driggers PH, Levi BZ et al. (1992). Mol Cell Biol 12: 38–44.

  • Galvin KM, Shi Y . (1997). Mol Cell Biol 17: 3723–3732.

  • Gordon S, Akopyan G, Garban H, Bonavida B . (2006). Oncogene 25: 1125–1142.

  • Hynes RO . (2002). Cell 110: 673–687.

  • Judware R, Culp LA . (1995). Oncogene 11: 2599–2607.

  • Judware R, Culp LA . (1997). Clin Exp Metast 15: 228–238.

  • Kawashima A, Kawahara E, Tokuda R, Nakanishi I . (2001). Cell Biol Int 25: 319–329.

  • Lee TC, Zhang Y, Schwartz RJ . (1994). Oncogene 4: 1047–1052.

  • Napoli C, Quehenberger O, De Nigris F, Abete P, Glass CK, Palinski W . (2000). FASEB J 14: 1996–2007.

  • Napoli C, Lerman LO, de Nigris F, Sica V . (2002). Neoplasia 4: 185–190.

  • Parise LV, Lee J, Juliano RL . (2000). Semin Cancer Biol 10: 407–414.

  • Pignatelli M, Hanby AM, Stamp GW . (1991). J Pathol 165: 25–32.

  • Pulverer BJ, Fisher C, Vousden K, Littlewood T, Evan G, Woodgett JR . (1994). Oncogene 9: 59–70.

  • Riggs KJ, Saleque S, Wong KK, Merrell KT, Lee JS, Shi Y et al. (1993). Mol Cell Biol 12: 7487–7495.

  • Schwartz MA . (1993). Cancer Res 53: 1503–1506.

  • Schwartz MA, Schaller MD, Ginsberg MH . (1995). Annu Rev Cell Dev Biol 11: 549–599.

  • Seales EC, Jurado GA, Singhal A, Bellis SL . (2003). Oncogene 22: 7137–7145.

  • Seales EC, Jurado GA, Brunson BA, Wakefield JK, Frost AR, Bellis SL . (2005). Cancer Res 65: 4645–4652.

  • Shang Y, Hu X, Di Renzo J, Lazar MA, Brown M . (2000). Cell 103: 843–852.

  • Shrivastava A, Calame L . (1994). Nucleic Acid Res 22: 5151–5155.

  • Thomas MJ, Seto E . (1999). Gene 236: 197–208.

  • Wang F, Hansen RK, Radisky D, Yoneda T, Barcellos-Hoff MH, Peterson OW et al. (2002). J Natl Cancer Inst 94: 1494–1503.

  • Weaver VM, Petersen OW, Wang F, Larabell CA, Briand P, Damsky C et al. (1997). J Cell Biol 137: 231–245.

  • Workman JL, Kingston RE . (1998). Annu Rev Biochem 67: 545–579.

  • Ye J, Cippitelli M, Dorman L, Ortaldo JR, Young HA . (1996). Mol Cell Biol 16: 4744–4753.

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Acknowledgements

We thank Dr L Altucci for collaborating in some FACS experiments, Dr O Pignalosa for help in some Western blot experiments, Drs L Mita and G Balzano for technical assistance in some EMSA experiments and Professor C Abbondanza, Mrs L Rossi, L Gallo, C Fiorito and G Graziano for cell cultures. We also thank Dr F Kavanagh for revising some sections of the paper. The present work was supported by National Research Funds from Regione Campania (Legge 5), Fondazione Banco di Napoli and ‘Ricerca di Ateneo 2005’ to Professor Vincenzo Sica and Professor Claudio Napoli.

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Authors and Affiliations

  1. Department of General Pathology, Division of Clinical Pathology, 1st School of Medicine, II University of Naples, Naples, Italy

    F de Nigris, C Botti, V Sica & C Napoli

  2. Division of Human Pathology, 1st School of Medicine, II University of Naples, Naples, Italy

    R Rossiello

  3. Department of Internal Medicine, Berkshire Medical Center, Pittsfield, MA, USA

    E Crimi

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  1. F de Nigris
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  2. C Botti
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  3. R Rossiello
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  4. E Crimi
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  5. V Sica
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  6. C Napoli
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Correspondence to C Napoli.

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de Nigris, F., Botti, C., Rossiello, R. et al. Cooperation between Myc and YY1 provides novel silencing transcriptional targets of α3β1-integrin in tumour cells. Oncogene 26, 382–394 (2007). https://doi.org/10.1038/sj.onc.1209804

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