The effect of BACH1 on malignant transformation of tumor

• Project/Area Number: 16K07108
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Tohoku University
• Principal Investigator: Matsumoto Mitsuyo 東北大学, 医学系研究科, 助教 (80400448)
• Research Collaborator: SATO masaki ; IGARASHI kazuhiko
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: BACH1 / 癌 / Bach1 / 線維芽細胞 / がん制御遺伝子

Outline of Final Research Achievements

BTB and CNC homolog 1 (BACH1) promotes transformation, cell proliferation and tumor formation in a model of activated RAS transfected-mouse embryonic fibroblasts (MEFs). We focused on the role of BACH1 in the pancreatic ductal adenocarcinoma (PDAC) more than 90% of which has KRAS mutation. Although BACH1 did not affect cell proliferation and tumor growth, but promoted migration ability and invasion ability in vitro and metastasis in vivo. We revealed that BACH1 repressed directly the expression of multiple epithelial-related genes as its mechanism. We showed also BACH1 is a poor prognostic factor on PDAC.

Academic Significance and Societal Importance of the Research Achievements

膵癌は最も予後不良な悪性腫瘍の１つである。その原因の１つである腫瘍の悪性形質転換の機序については未だ未解明な点も多い。本研究から腫瘍の悪性形質転換のステップと考えられている上皮間葉転換を、BACH1が直接複数の上皮系遺伝子の転写を抑制することで促すことが示唆された。実際にBACH1高発現膵癌患者の予後は不良であり、BACH1が膵癌の治療標的となり得る可能性を示した点で、その意義は高いと考える。

Research Products

• [Journal Article] Infection perturbs Bach2- and Bach1-dependent erythroid lineage chioce to cause anemia (2018)
  • Author(s): Kato H, Itoh-Nakadai A, Matsumoto M, Ishii Y, Watanabe-Matsui M, Ikeda M, Ebina-Shibuya R, Sato Y, Kobayashi M, Nishizawa H, Suzuki K, Muto A, Fujiwara T, Nannya Y, Cazzola M, Ogawa S, Harigae H, Igarashi K
  • Journal Title: Nat Immunol Volume: 19 Issue: 10 Pages: 496-497
  • DOI: 10.1038/s41590-018-0202-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Bach2 Promotes B Cell Receptor?Induced Proliferation of B Lymphocytes and Represses Cyclin-Dependent Kinase Inhibitors (2018)
  • Author(s): Miura Yuichi、Morooka Mizuho、Sax Nicolas、Roychoudhuri Rahul、Itoh-Nakadai Ari、Brydun Andrey、Funayama Ryo、Nakayama Keiko、Satomi Susumu、Matsumoto Mitsuyo、Igarashi Kazuhiko、Muto Akihiko
  • Journal Title: J Immunol Volume: - Issue: 8 Pages: 2882-2893
  • DOI: 10.4049/jimmunol.1601863
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Phosphorylation of BACH1 switches its function from transcription factor to mitotic chromosome regulator and promotes its interaction with HMMR. (2018)
  • Author(s): Li J, Shima H, Nishizawa H, Ikeda M, Brydun A, Matsumoto M, Kato H, Saiki Y, Liu L, Watanabe-Matsui M, Iemura K, Tanaka K, Shiraki T, Igarashi K.
  • Journal Title: Biochemical Journal Volume: 475 Issue: 5 Pages: 981-1002
  • DOI: 10.1042/bcj20170520
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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] Inflammatory responses induce an identity crisis of alveolar macrophages, leading to pulmonary alveolar proteinosis. (2017)
  • Author(s): Ebina-Shibuya R, Matsumoto M, Kuwahara M, Jang KJ, Sugai M, Ito Y, Funayama R, Nakayama K, Sato Y, Ishii N, Okamura Y, Kinoshita K, Kometani K, Kurosaki T, Muto A, Ichinose M, Yamashita M, Igarashi K.
  • Journal Title: The Journal of biological chemistry Volume: 292 Issue: 44 Pages: 18098-18112
  • DOI: 10.1074/jbc.m117.808535
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The mTOR-Bach2 Cascade Controls Cell Cycle and Class Switch Recombination during B Cell Differentiation. (2017)
  • Author(s): Tamahara T, Ochiai K, Muto A, Kato Y, Sax N, Matsumoto M, Koseki T, Igarashi K.
  • Journal Title: Molecular and cellular biology Volume: 37 Issue: 24
  • DOI: 10.1128/mcb.00418-17
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 転写因子Bach1による酸化ストレス依存メラノーマ細胞増殖抑制機序 (2017)
  • Author(s): 松本光代、ブリドンアンドレイ、熊谷さやか、五十嵐和彦
  • Organizer: 生命科学系学会合同年次大会
• [Remarks] 東北大学大学院 医学系研究科 生物化学分野/成果情報
  • URL: http://www.biochem.med.tohoku.ac.jp/category/report/
• [Patent(Industrial Property Rights)] 新規膵臓癌上皮間葉移行マーカー (2019)
  • Inventor(s): 五十嵐和彦、松本光代、佐藤正規、西澤弘成
  • Industrial Property Rights Holder: 五十嵐和彦、松本光代、佐藤正規、西澤弘成
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019
  • Overseas