2009 Fiscal Year Final Research Report
Anticancer drug discovery based on regulation of chromatin structure and function
Project/Area Number |
17016080
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Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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Allocation Type | Single-year Grants |
Review Section |
Biological Sciences
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Research Institution | The Institute of Physical and Chemical Research |
Principal Investigator |
YOSHIDA Minoru The Institute of Physical and Chemical Research, 吉田化学遺伝学研究室, 主任研究員 (80191617)
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Co-Investigator(Kenkyū-buntansha) |
YASHIRODA Yoko 独立行政法人理化学研究所, 吉田化学遺伝学研究室, 専任研究員 (60360658)
NISHINO Norikazu 九州工業大学, 大学院・生命体工学研究科, 教授 (40145165)
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Co-Investigator(Renkei-kenkyūsha) |
YANORI Takao 財団法人癌研究会, 癌化学療法センター分子薬理部, 部長 (60200854)
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Project Period (FY) |
2005 – 2009
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Keywords | ヒストン / アセチル化 / メチル化 / SUMO化 / ケミカルゲノミクス / ドラックデザイン / スプライシング / エピジェネティクス |
Research Abstract |
It has been shown that regulation of chromatin structure and function including histone acetylation is involved in tumorigenesis. In this study, we aimed to identify factors responsible for chromatin regulation and develop their inhibitors. We succeeded in developing Ky-2, a new HDAC inhibitor exhibiting strong antitumor activity, the first splicing inhibitor spliceostatin A that affects chromatin structure, and a novel fluorescent imaging probe that allows detection of histone acetylation in living cells.
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Research Products
(59 results)
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[Journal Article] Bicyclic peptides as potent inhibitors of histone deacetylases: Optimization of alkyl loop length.2010
Author(s)
Islam, N.M., Kato, T., Nishino, N., Kim, H. -J., Ito, A., Yoshida, M.
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Journal Title
Bioorg. Med. Chem. Lett. 20
Pages: 997-999
Peer Reviewed
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[Journal Article] Total synthesis of the bicyclic depsipeptide HDAC inhibitors spiruchostatins A and B, 5''-epi-spiruchostatin B, FK228 (FR901228) and preliminary evaluation of their biological activity.2009
Author(s)
Narita, K., Kikuchi, T., Watanabe, K., Takizawa, T., Oguchi, T., Kudo, K., Matsuhara, K., Abe, H., Yamori, T., Yoshida, M., Katoh, T.
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Journal Title
Chemistry 15
Pages: 11174-11186
Peer Reviewed
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[Journal Article] JBIR-17, a novel trichostatin analogue from Streptomyces sp. 26634.2009
Author(s)
Ueda, J. -y., Hwang, J. -H., Kato, T., Ochiai, A., Isshiki, K., Yoshida, M., Takagi, M., Shin-ya, K.
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Journal Title
J. Antibiotics 62
Pages: 283-285
Peer Reviewed
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[Journal Article] The protein farnesyltransferase regulates HDAC6 activity in a microtubule-dependent manner.2009
Author(s)
Zhou, J., Vos, C.C., Gjyrezi, A., Yoshida, M., Khuri, F.R., Tamanoi, F., Giannakakou, P.
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Journal Title
J. Biol. Chem. 284
Pages: 9648-9655
Peer Reviewed
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[Journal Article] New Rev-export inhibitor from Alpinia galanga and structure-activity relationship.2009
Author(s)
Tamura, S., Shiomi, A., Kaneko, M., Ye, Y., Yoshida, M., Yoshikawa, M., Kimura, T., Kobayashi, M., Murakami, N.
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Journal Title
Bioorg. Med. Chem. Lett. 19
Pages: 2555-2557
Peer Reviewed
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[Journal Article] A molecular barcoded yeast ORF library enables mode-of-action analysis of bioactive compounds.2009
Author(s)
Ho, C.H., Magtanong, L., Barker, S.L., Gresham, D., Nishimura, S., Natarajan, P., Koh, J.L.Y., Proter, J., Gray, C.A., Andersen, R.J., Giaever, G., Nislow, C., Andrews, B., Botstein, D., Graham, T.R., Yoshida, M., Boone, C.
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Journal Title
Nature Biotechnol. 27
Pages: 369-377
Peer Reviewed
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[Journal Article] Ginkgolic acid inhibits protein SUMOylation by blocking formation of the E1-SUMO intermediate.2009
Author(s)
Fukuda, I., Ito, A., Hirai, G., Nishimura, S., Kawasaki, H., Saitoh, H., Kimura, K. -i., Sodeoka, M., Yoshida, M.
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Journal Title
Chem. Biol. 16
Pages: 133-140
Peer Reviewed
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[Journal Article] Kerriamycin B inhibits protein SUMOylation.2009
Author(s)
Fukuda, I., Ito, A., Uramoto, M., Saitoh, H., Kawasaki, H., Osada, H., Yoshida, M.
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Journal Title
J. Antibiotics 62
Pages: 221-224
Peer Reviewed
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[Journal Article] Interaction of aliphatic cap group in inhibition of histone deacetylases by cyclic tetrapeptides.2008
Author(s)
Nishino, N., Shivashimpi, G.M., Soni, P.B., Bhuiyan, M.P.I., Kato, T., Maeda, S., Nishino, T.G., Yoshida, M.
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Journal Title
Bioorg. Med. Chem. 16
Pages: 437-445
Peer Reviewed
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[Journal Article] Evaluation of antiangiogenic activity of azumamides by the in vitro vascular organization model using mouse-induced pluripotent stem (iPS) cells.2008
Author(s)
Nakao, Y., Narazaki, G., Hoshino, T., Maeda, S., Yoshida, M., Maejima, H., Yamashita, J.K.
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Journal Title
Bioorg. Med. Chem. Lett. 18
Pages: 2982-2984
Peer Reviewed
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[Journal Article] Bach1 inhibits oxidative stress-induced cellular senescence by impeding p53 function on chromatin. Nature Struct.2008
Author(s)
Dohi, Y., Ikura, T., Hoshikawa, Y., Katoh, Y., Ota, K., Nakanome, A., Muto, A., Omura, S., Ohta, T., Ito, A., Yoshida, M., Noda, T., Igarashi, K.
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Journal Title
Mol. Biol. 15
Pages: 1246-1254
Peer Reviewed
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[Journal Article] Characterisation of the in vitro activity of the depsipeptide histone deacetylase inhibitor spiruchostatin A.2008
Author(s)
Crabb, S.J., Howell, M., Rogers, H., Ishfaq, M., Yurek-George, A., Carey, K., Pickering, B.M., East, P., Mitter, R., Maeda, S., Johnson, P.W., Townsend, P., Shin-ya, K., Yoshida, M., Ganesan, A., Packham, G.
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Journal Title
Biochem. Pharmacol. 76
Pages: 463-475
Peer Reviewed
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[Journal Article] Combined effects of p53 gene therapy and leptomycin B in human esophageal squamous cell carcinoma.2008
Author(s)
Hoshino, I., Matsubara, H., Komatsu, A., Akutsu, Y., Nishimori, T., Yoneyama, Y., Murakami, K., Sakata, H., Matsushita, K., Miyazawa, Y., Brooks, R., Yoshida, M., Ochiai, T.
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Journal Title
Oncology 75
Pages: 113-119
Peer Reviewed
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[Journal Article] Effects of downregulated HDAC6 expression on the proliferation of lung cancer cells. Biochem.2008
Author(s)
Kamemura, K., Ito, A., Shimazu, T., Matsuyama, A., Maeda, S., Yao, T. -P., Horinouchi, S., Khochbin, S., Yoshida, M.
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Journal Title
Biophys. Res. Commun. 374
Pages: 84-89
Peer Reviewed
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[Journal Article] 14-3-3 regulates the nuclear import of class IIa histone deacetylases.2008
Author(s)
Nishino, T.G., Miyazaki, M., Hoshino, H., Miwa, Y., Horinouchi, S., Yoshida, M.
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Journal Title
Biochem. Biophys. Res. Commun. 377
Pages: 852-856
Peer Reviewed
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[Journal Article] Inhibition of splicing and nuclear retention of pre-mRNA by spliceostatin A in fission yeast.2007
Author(s)
Lo, C. -W., Kaida, D., Nishimura, S., Matsuyama, A., Yashiroda, Y., Taoka, H., Ishigami, K., Watanabe, H., Nakajima, H., Tani, T., Horinouchi, S., Yoshida, M.
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Journal Title
Biochem. Biophys. Res. Commun. 364
Pages: 573-577
Peer Reviewed
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[Journal Article] Molecular design of histone deacetylase inhibitors by aromatic ring shifting in chlamydocin framework.2007
Author(s)
Shivashimpi, G.M., Amagai, S., Kato, T., Nishino, N., Maeda, S., Nishino, T.G., Yoshida, M.
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Journal Title
Bioorg. Med. Chem. 15
Pages: 7830-7839
Peer Reviewed
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[Journal Article] Design, synthesis, and evaluation of isoindolinone-hydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors.2007
Author(s)
Lee, S., Shinji, C., Ogura, K., Shimizu, M., Maeda, S., Sato, M., Yoshida, M., Hashimoto, Y., Miyachi, H.
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Journal Title
Bioorg. Med. Chem. Lett. 17
Pages: 4895-4900
Peer Reviewed
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[Journal Article] Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA.2007
Author(s)
Kaida, D., Motoyoshi, H., Tashiro, E., Nojima, T., Hagiwara, M., Ishigami, K., Watanabe, H., Kitahara, T., Yoshida, T., Nakajima, H., Tani, T., Horinouchi, S., Yoshida, M.
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Journal Title
Nature Chem. Biol. 3
Pages: 576-583
Peer Reviewed
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[Journal Article] The first biologically active synthetic analogues of FK228, the depsipeptide histone deacetylase inhibitor.2007
Author(s)
Yurek-George, A., Cecil, A.R.L., Mo, A.H.K., Wen, S., Rogers, H., Habens, F., Maeda, S., Yoshida, M., Packham, G., Ganesan, A.
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Journal Title
J. Med. Chem. 50
Pages: 5720-5726
Peer Reviewed
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[Journal Article] Corepressor SMRT and class II histone deacetylases promote Bach2 nuclear retention and formation of nuclear foci that are responsible for local transcriptional repression.2007
Author(s)
Hoshino, H., Nishino, T.G., Tashiro, S., Miyazaki, M., Ohmiya, Y., Igarashi, K., Horinouchi, S., Yoshida, M.
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Journal Title
J. Biochem. (Tokyo) 141
Pages: 719-727
Peer Reviewed
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[Journal Article] Bone morphogenetic protein-2 stimulates Runx2 acetylation.2006
Author(s)
Jeon, E. -J., Lee, K. -Y., Choi, N. -S., Lee, M. -H., Kim, H. -N., Jin, Y. -H., Ryoo, H. -M., Choi, J. -Y., Yoshida, M., Nishino, N., Oh, B. -C., Lee, K. -S., Lee, Y.H., Bae, S. -C.
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Journal Title
J. Biol. Chem. 281
Pages: 16502-16511
Peer Reviewed
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[Journal Article] Nucleolin is involved in interferon Regulatory Factor-2 dependent transcriptional activation.2006
Author(s)
Masumi, A., Fukazawa, H., Shimazu, T., Yoshida, M., Ozato, K., Komuro, K., Yamaguchi, K.
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Journal Title
Oncogene 25
Pages: 5113-5124
Peer Reviewed
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[Journal Article] Regulation of SV40 large T antigen stability by reversible acetylation.2006
Author(s)
Shimazu, T., Komatsu, Y., Nakayama, K.I., Fukazawa, H., Horinouchi, S., Yoshida, M.
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Journal Title
Oncogene 25
Pages: 7391-7400
Peer Reviewed
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[Journal Article] ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe.2006
Author(s)
Matsuyama, A., Arai, R., Yashiroda, Y., Shirai, A., Kamata, A., Sekido, S., Kobayashi, Y., Hashimoto, A., Hamamoto, M., Hiraoka, Y., Horinouchi, S., Yoshida, M.
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Journal Title
Nature Biotechnol. 24
Pages: 841-847
Peer Reviewed
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[Journal Article] Nucleocytoplasmic transport of fluorescent mRNA in living mammalian cells: nuclear mRNA export is coupled to ongoing gene transcription.2006
Author(s)
Tokunaga, K., Shibuya, T., Ishihama, Y., Tadakuma, H., Ide, M., Yoshida, M., Funatsu, T., Ohshima, Y., Tani, T.
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Journal Title
Genes Cells 11
Pages: 305-317
Peer Reviewed
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[Journal Article] Chlamydocin analogs bearing carbonyl group as possible ligand toward zinc atom in histone deacetylases.2006
Author(s)
Bhuiyan, M.P., Kato, T., Okauchi, T., Nishino, N., Maeda, S., Nishino, T.G., Yoshida, M.
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Journal Title
Bioorg. Med. Chem. 14
Pages: 3438-3446
Peer Reviewed
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[Journal Article] Induction of a ribotoxic stress response that stimulates stress-activated protein kinases by 13-deoxytedanolide, an antitumor marine macrolide. Biosci.2006
Author(s)
Lee, K. -H., Nishimura, S., Matsunaga, S., Fusetani, N., Ichijo, H., Horinouchi, S., Yoshida, M.
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Journal Title
Biotechnol. Biochem. 69
Pages: 161-171
Peer Reviewed
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[Journal Article] Design, synthesis, and evaluation of cyclic amide/imide-bearing hydroxamic acid derivatives as class-selective histone deacetylase (HDAC) inhibitors.2006
Author(s)
Shinji, C., Maeda, S., Imai, K., Yoshida, M., Hashimoto, Y., Miyachi, H.
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Journal Title
Bioorg Med Chem. 14
Pages: 7625-7651
Peer Reviewed
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[Journal Article] Highly potent and selective histone deacetylase 6 inhibitors designed based on a small-molecular substrate.2006
Author(s)
Suzuki, T., Kouketsu, A., Itoh, Y., Hisakawa, S., Maeda, S., Yoshida, M., Nakagawa, H., Miyata, N.
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Journal Title
J Med. Chem. 49
Pages: 4809-4812
Peer Reviewed
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[Journal Article] Sichuan pepper extracts block the PAK1/Cyclin D1 pathway and the growth of NF1-deficient cancer xenograft in mice.2006
Author(s)
Hirokawa, Y., Nheu, T., Grimm, K., Mautner, V., Maeda, S., Yoshida, M., Komiyama, K., Maruta, H.
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Journal Title
Cancer Biol Ther 5
Pages: 305-309
Peer Reviewed
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[Journal Article] Nuclear-cytoplasmic shuttling of a RING-IBR protein RBCK1 and its functional interaction with nuclear body proteins.2005
Author(s)
Tatematsu, K., Yoshimoto, N., Koyanagi, T., Tokunaga, C., Tachibana, T., Yoneda, Y., Yoshida, M., Okajima, T., Tanizawa, K., Kuroda, S. i.
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Journal Title
. Biol. Chem. 280
Pages: 22937-22944
Peer Reviewed
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[Journal Article] HIV-Tat targets Tip60 to impair the apoptotic cell response to genotoxic stresses.2005
Author(s)
Col, E., Caron, C., Chable-Bessia, C., Legube, G., Gazzeri, S., Komatsu, Y., Yoshida, M., Benkirane, M., Trouche, D., Khochbin, S.
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Journal Title
EMBO J. 24
Pages: 2634-2645
Peer Reviewed
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[Journal Article] Inhibition of protein synthesis and activation of stress-activated protein kinases by onnamide A and theopederin B, antitumor marine natural products.2005
Author(s)
Lee, K. -H., Nishimura, S., Matsunaga, S., Fusetani, N., Horinouchi, S., Yoshida, M.
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Journal Title
Cancer Sci. 96
Pages: 357-364
Peer Reviewed
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[Journal Article] T. -P. HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor.2005
Author(s)
Kovacs, J.J., Murphy, P.J.M., Gaillard, S., Zhao, X., Wu, J. -T., Nicchitta, C.V., Yoshida, M., Toft, D.O., Pratt, W.B., Yao
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Journal Title
Mol. Cell 18
Pages: 601-607
Peer Reviewed
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[Journal Article] Design and synthesis of phthalimide-type histone deacetylase inhibitors.2005
Author(s)
Shinji, C., Nakamura, T., Maeda, S., Yoshida, M., Hashimoto, Y., Miyachi, H.
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Journal Title
Bioorg Med Chem Lett. 15
Pages: 4427-4431
Peer Reviewed
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[Journal Article] Significance of HDAC6 regulation via estrogen signaling for cell motility and prognosis in estrogen receptor-positive breast cancer.2005
Author(s)
Saji, S., Kawakami, M., Hayashi, S.I., Yoshida, N., Hirose, M., Horiguchi, S.I., Itoh, A., Funata, N., Schreiber, S.L., Yoshida, M., Toi, M.
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Journal Title
Oncogene 24
Pages: 4531-4539
Peer Reviewed
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