Abstract
Transformation of fibroblasts with the v-fos oncogene produces a highly invasive phenotype that is mediated by changes in gene expression. Inhibition of histone deacetylase (HDAC) activity with trichostatin A (TSA) or valproic acid (VPA) at concentrations that do not affect morphology, motility, chemotaxis or proliferation, strongly inhibits invasion and results in the re-expression of a significant proportion of those genes that are downregulated in the v-Fos-transformed cells. Independent expression of three of these re-expressed genes, (Ring1 and YY1 binding protein (RYBP); protocadherin gamma subfamily C,3 (PCDHGC3); and signal transducer and activator of transcription 6 (STAT6)) in Fos-transformed cells, has no effect on morphology, motility, chemotaxis or proliferation, but strongly inhibits invasion. Therefore, we conclude that the ability of v-Fos-transformed cells to invade is dependent upon repression of gene expression through either direct or indirect HDAC activity.
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References
Bakin AV and Curran T . (1999). Science, 283, 387–390.
Buttner C, Skupin A and Rieber EP . (2004). J Cell Physiol, 198, 248–258.
Eferl R and Wagner E . (2003). Nat Rev Cancer, 3, 859–868.
Garcia E, Marcos-Gutierrez C, del Mar Lorente M, Moreno JC and Vidal M . (1999). EMBO J, 18, 3404–3418.
Gottlicher M, Minucci S, Zhu P, Kramer OH, Schimpf A, Giavara S, Sleeman JP, Lo Coco F, Nervi C, Pelicci PG and Heinzel T . (2001). EMBO J, 20, 6969–6978.
Grunstein M . (1997). Nature, 389, 349–352.
Hennigan RF, Hawker KL and Ozanne BW . (1994). Oncogene, 9, 3591–3600.
Imai T, Adachi S, Nishijo K, Ohgushi M, Okada M, Yasumi T, Watanabe K, Nishikomori R, Nakayama T, Yonehara S, Toguchida J and Nakahata T . (2003). Oncogene, 22, 9231–9242.
Johnston IM, Spence HJ, Winnie JN, McGarry L, Vass JK, Meagher L, Stapleton G and Ozanne BW . (2000). Oncogene, 19, 5348–5358.
Kelly WK, O'Connor OA and Marks PA . (2002). Expert Opin Invest Drugs, 11, 1695–1713.
Kouzarides T . (2000). EMBO J, 19, 1176–1179.
Kuo MH and Allis CD . (1998). Bioessays, 20, 615–626.
Kwon HJ, Owa T, Hassig CA, Shimada J and Schreiber SL . (1998). Proc Natl Acad Sci USA, 95, 3356–3361.
Lamb RF, Hennigan RF, Turnbull K, Katsanakis KD, MacKenzie ED, Birnie GD and Ozanne BW . (1997a). Mol Cell Biol, 17, 963–976.
Lamb RF, Ozanne BW, Roy C, McGarry L, Stipp C, Mangeat P and Jay DG . (1997b). Curr Biol, 7, 682–688.
Lehrmann H, Pritchard LL and Harel-Bellan A . (2002). Adv Cancer Res, 86, 41–65.
Liu LT, Chang HC, Chiang LC and Hung WC . (2003). Cancer Res, 63, 3069–3072.
Marks PA, Miller T and Richon VM . (2003). Curr Opin Pharmacol, 3, 344–351.
Masui T, Doi R, Koshiba T, Fujimoto K, Tsuji S, Nakajima S, Koizumi M, Toyoda E, Tulachan S, Ito D, Kami K, Mori T, Wada M, Noda M and Imamura M . (2003). Clin Cancer Res, 9, 1779–1784.
Matsumoto M, Matsutani S, Sugita K, Yoshida H, Hayashi F, Terui Y, Nakai H, Uotani N, Kawamura Y, Matsumoto K, Shoji J and Yoshida T . (1992). J Antibiotics (Tokyo), 45, 879–885.
McGaha TL, Le M, Kodera T, Stoica C, Zhu J, Paul WE and Bona CA . (2003). Arthritis Rheum, 48, 2275–2284.
Ozanne BW, McGarry L, Spence HJ, Johnston I, Winnie J, Meagher L and Stapleton G . (2000). Eur J Cancer, 36, 1640–1648.
Quelle FW, Shimoda K, Thierfelder W, Fischer C, Kim A, Ruben SM, Cleveland JL, Pierce JH, Keegan AD, Nelms K, Paul WE and Ihle JN . (1995). Mol Cell Biol, 15, 3336–3343.
Rosato RR, Almenara JA and Grant S . (2003). Cancer Res, 63, 3637–3645.
Sambrook J, Fritsch EF and Maniatis T . (1989). Molecular Cloning. A Laboratory Manual, 2 edn Cold Spring Harbour Laboratory Press: Cold Spring Harbor, NY.
Sano K, Tanihara H, Heimark RL, Obata S, Davidson M, St John T, Taketani S and Suzuki S . (1993). EMBO J, 12, 2249–2256.
Schlisio S, Halperin T, Vidal M and Nevins JR . (2002). EMBO J, 21, 5775–5786.
Scott LA, Vass JK, Parkinson EK, Gillespie DAF, Winnie JN and Ozanne BW . (2004). Mol Cell Biol, 24, 1540–1559.
Spence HJ, Johnston I, Ewart K, Buchanan SJ, Fitzgerald U and Ozanne BW . (2000). Oncogene, 19, 1266–1276.
Stapleton G, Malliri A and Ozanne BW . (2002). J Cell Sci, 115, 2713–2724.
Sugita K, Yoshida H, Matsumoto M and Matsutani S . (1992). Biochem Biophys Res Commun, 182, 379–387.
Suzuki ST . (2000). Exp Cell Res, 261, 13–18.
Timmermann S, Lehrmann H, Polesskaya A and Harel-Bellan A . (2001). Cell Mol Life Sci, 58, 728–736.
Trimarchi JM, Fairchild B, Wen J and Lees JA . (2001). Proc Natl Acad Sci USA, 98, 1519–1524.
Yamashita Y, Shimada M, Harimoto N, Rikimaru T, Shirabe K, Tanaka S and Sugimachi K . (2003). Int J Cancer, 103, 572–576.
Yoshida M, Kijima M, Akita M and Beppu T . (1990). J Biol Chem, 265, 17174–17179.
Zhang Y, Iratni R, Erdjument-Bromage H, Tempst P and Reinberg D . (1997). Cell, 89, 357–364.
Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A and Reinberg D . (1999). Genes Dev, 13, 1924–1935.
Acknowledgements
We thank Linda Scott, Heather Spence, Genevieve Stapleton and David Gillespie for helpful discussion; Margaret O'Prey and Peter McHardy for technical help with imaging; and Robert McFarlane and Christine Lang for PCR primer synthesis and DNA sequencing. We also thank Tony Kouzarides, Wellcome/CRUK Institute and Department of Pathology, Cambridge, UK, for helpful discussion; and Miguel Vidal, Centro De Investigaciones Biologicas, Madrid, Spain; James Ihle, St Jude Children's Research Hospital, Memphis, USA; and Shintaro T Suzuki, Kwanseigakuin University, Hyogo, Japan for gifts of cDNAs. This work was funded by Cancer Research UK.
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McGarry, L., Winnie, J. & Ozanne, B. Invasion of v-FosFBR-transformed cells is dependent upon histone deacetylase activity and suppression of histone deacetylase regulated genes. Oncogene 23, 5284–5292 (2004). https://doi.org/10.1038/sj.onc.1207687
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DOI: https://doi.org/10.1038/sj.onc.1207687
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