Verification of genomic diversity required for tumorigenesis

• Project/Area Number: 16K14664
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Molecular biology
• Research Institution: Tohoku University
• Principal Investigator: NAKAYAMA Keiko 東北大学, 医学系研究科, 教授 (60294972)
• Co-Investigator(Kenkyū-buntansha): 城田 松之 東北大学, 医学系研究科, 助教 (00549462) ; 舟山 亮 東北大学, 医学系研究科, 助教 (20452295) ; 細金 正樹 東北大学, 医学系研究科, 助手 (30734347)
• Project Period (FY): 2016-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: ゲノム編集 / CRISPR/Cas9システム / 超並列シークエンス解析 / 腫瘍形成能 / Geminin / エピゲノム / 細胞周期 / ES細胞 / Cdt1 / エピゲム / 転写制御 / MLL2

Outline of Final Research Achievements

CRISPR/Cas9 library was introduced to NIH3T3 cells and MDA-MD-468 cells to generate cell library which are gene disrupted. Groups of cells which was disrupted a gene by CRISPR/Cas9 system were obtained. These cells were inoculated subcutaneously on the back of immunodeficient mice to grow tumors. Even NIH3T3 cells which were introduced library failed to stable tumorigenesis as well as wild type cells. These data suggested that NIH3T3 population containing different kinds of a single gene disrupted cells did not achieve capability of tumorigenesis. With MDA-MD-462 cells, we observed cells introduced CRISPR/Cas9 library gain function of tumorigenesis compared to wild-type cells.

Research Products

• [Journal Article] Geminin is an indispensable inhibitor of Cdt1 in mouse embryonic stem cells. (2017)
  • Author(s): Hosogane, M., Bosu, L., Fukumoto, E., Yamada, H., Sato, S., Nakayama, K.
  • Journal Title: Genes Cells Volume: 印刷中 Issue: 4 Pages: 360-375
  • DOI: 10.1111/gtc.12482
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A Bach2-Cebp gene regulatory network for the commitment of multipotent hematopoietic progenitors. (2017)
  • Author(s): Itoh-Nakadai, A., Matsumoto, M., Kato, H., Sasaki, J., Uehara, Y., Sato, Y., Ebina-Shibuya, R., Morooka, M., Funayama, R., Nakayama, K., Ochiai, K., Muto, A. and Igarashi, K.
  • Journal Title: Cell Reports Volume: 18 Issue: 10 Pages: 2401-2414
  • DOI: 10.1016/j.celrep.2017.02.029
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A large-scale targeted proteomics assay resource based on an in vitro human proteome. (2017)
  • Author(s): Matsumoto M, Matsuzaki F, Oshikawa K, Goshima N, Mori M, Kawamura Y, Ogawa K, Fukuda E, Nakatsumi H, Natsume T, Fukui K, Horimoto K, Nagashima T, Funayama R, Nakayama K, Nakayama KI.
  • Journal Title: Nat Methods Volume: 14 Issue: 3 Pages: 251-258
  • DOI: 10.1038/nmeth.4116
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Regulatory signatures of liver regeneration distilled by integrative analysis of mRNA, histone methylation, and proteomics. (2017)
  • Author(s): Sato, Y., Katoh, Y., Matsumoto, M., Sato, M., Ebina, M., Itoh-Nakadai, A., Funayama, R., Nakayama, K., Unno, M., Igarashi, K.
  • Journal Title: J.Biol.Chem. Volume: 印刷中 Issue: 19 Pages: 8019-8037
  • DOI: 10.1074/jbc.m116.774547
  • Peer Reviewed / Open Access
• [Journal Article] Exome sequencing deciphers a germline MET mutation in familial epidermal growth factor receptor-mutant lung cancer. (2017)
  • Author(s): Tode N, Kikuchi T, Sakakibara T, Hirano T, Inoue A, Ohkouchi S, Tamada T, Okazaki T, Koarai A, Sugiura H, Niihori T, Aoki Y, Nakayama K, Matsumoto K, Matsubara Y, Yamamoto M, Watanabe A, Nukiwa T, Ichinose M.
  • Journal Title: Cancer Sci Volume: 印刷中 Issue: 6 Pages: 1263-1270
  • DOI: 10.1111/cas.13233
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The aryl hydrocarbon receptor AhR links atopic dermatitis and air pollution via induction of the neurotrophic factor artemin. (2017)
  • Author(s): Hidaka, T., Ogawa, E., Kobayashi, E.H., Suzuki, T., Funayama, R., Nagashima, T., Fujimura, T., Aiba, S., Nakayama, K., Okuyama, R., Yamamoto, M.
  • Journal Title: Nat. Immunol. Volume: 18 Issue: 1 Pages: 64-73
  • DOI: 10.1038/ni.3614
  • Peer Reviewed
• [Journal Article] The SCFβ-TRCP E3 ubiquitin ligase complex targets Lipin1 for ubiquitination and degradation to promote hepatic lipogenesis. (2017)
  • Author(s): Shimizu K, Fukushima H, Ogura K, Lien EC, Nihira NT, Zhang J, North BJ, Guo A, Nagashima K, Nakagawa T, Hoshikawa S, Watahiki A, Okabe K, Yamada A, Toker A, Asara JM, Fukumoto S, Nakayama KI, Nakayama K, Inuzuka H, Wei W.
  • Journal Title: Sci Signal. doi: 10.1126/scisignal.aah4117. Volume: 10 Issue: 460 Pages: 1-15
  • DOI: 10.1126/scisignal.aah4117
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Homeostatic Shift Facilitates Endoplasmic Reticulum Proteostasis through Transcriptional Integration of Proteostatic Stress Response Pathways. (2017)
  • Author(s): Baird L, Tsujita T, Kobayashi E, Funayama R, Nagashima T, Nakayama K, and Yamamoto M.
  • Journal Title: Mol Cell Biol Volume: 37 Issue: 4
  • DOI: 10.1128/mcb.00439-16
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Dramatic response after functional hemispherectomy in a patient with epileptic encephalopathy carrying a de novo COL4A1 mutation. (2017)
  • Author(s): Hino-Fukuyo, N., Kikuchi, A., Iwasaki, M., Sato, Y., Kubota, Y., Kobayashi, T., Nakayama, T., Haginoya, K., Arai-Ichinoi, N., Niihori, T., Sato, R., Suzuki, T., Kudo, H., Funayama, R., Nakayama, K., Aoki, Y., Kure, S.
  • Journal Title: Brain Dev. Volume: 39 Issue: 4 Pages: 337-340
  • DOI: 10.1016/j.braindev.2016.11.006
  • Peer Reviewed
• [Journal Article] Ubiquitylation of Ku80 by RNF126 Promotes Completion of Nonhomologous End Joining-Mediated DNA Repair. (2017)
  • Author(s): Ishida N, Nakagawa T, Iemura SI, Yasui A, Shima H, Katoh Y, Nagasawa Y, Natsume T, Igarashi K, Nakayama K.
  • Journal Title: Mol Cell Biol Volume: 37 Issue: 4
  • DOI: 10.1128/mcb.00347-16
  • Peer Reviewed
• [Journal Article] Wnt-beta-catenin signaling regulates ABCC3 (MRP3) transporter expression in colorectal cancer. (2016)
  • Author(s): Kobayashi, M., Funayama, R., Ohnuma, S., Unno, M., Nakayama, K.
  • Journal Title: Cancer Sci. Volume: 107 Issue: 12 Pages: 1776-1784
  • DOI: 10.1111/cas.13097
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Lack of genetic variation prevents adaptation at the geographic range margin in a damselfly. (2016)
  • Author(s): Takahashi, Y., Suyama, Y., Matsuki, Y., Funayama, R., Nakayama, K., Kawata, M.
  • Journal Title: Mol. Ecol. Volume: 25 Issue: 18 Pages: 4450-4460
  • DOI: 10.1111/mec.13782
  • Peer Reviewed
• [Presentation] Molecular analysis of Amyotrophic Lateral Sclerosis associated Cyclin F mutants. (2016)
  • Author(s): Yujiao Yu, Akane Morohoshi, Tadashi Nakagawa, Keiko Nakayama.
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-12-01
• [Presentation] ユビキチン化によるFACT複合体の機能制御 (2016)
  • Author(s): 諸星茜、中川直、中山啓子
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-12-01
• [Presentation] H3K27ヒストン修飾によるエンハンサー制御のゲノムワイド解析 (2016)
  • Author(s): 細金正樹、中山啓子
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-12-01
• [Presentation] 大腸がんにおけるタンパク質シトルリン化酵素PADI2の役割 (2016)
  • Author(s): 舟山亮、谷口肇、水間正道、藤島史喜、小林実、大沼忍、海野倫明、中山啓子
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-12-01
• [Presentation] Reactivation of cell proliferation by continuous TGF-β treatment. (2016)
  • Author(s): Tadashi Nakagawa, Masaki Hosogane, Ryo Funayama, Keiko Nakayama.
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-11-30
• [Presentation] 大腸癌で発現が抑制されるPeptidylarginine deiminase2の機能解析 (2016)
  • Author(s): 谷口肇、舟山亮、小林実、高館達之、阿部友哉、水間正道、藤島史喜、大沼忍、内藤剛、海野倫明、中山啓子
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-06
• [Remarks] 東北大学がん医学コアセンター細胞増殖制御分野
  • URL: http://www.devgen.med.tohoku.ac.jp/