Targeted disruption of the BCL9/beta-catenin complex in colorectal cancer using stapled peptide

• Project/Area Number: 23890169
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Sapporo Medical University
• Principal Investigator: TAKADA Kohichi 札幌医科大学, 医学部, 助教 (90398321)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 抗大腸癌ペプチド / BCL9 / Wnt シグナル / Wntシグナル

Research Abstract

We developed a stabilized a helix of BCL9 (SAH-BCL9), which we show targets beta-catenin, dissociates native beta-catenin/BCL9 complexes, selectively suppresses Wnt transcription, and exhibits mechanism-based antitumor effects. SAH-BCL9also suppresses tumor growth, angiogenesis, invasion, and metastasis in mouse xenograft models of Colo320 colorectal carcinoma. By inhibiting the BCL9/beta-catenin interaction and selectively suppressing oncogenic Wnt transcription, SAH-BCL9 may serve as a prototypetherapeutic agent for cancers driven by deregulated Wnt signaling.

Research Products

• [Journal Article] TRIM13(RFP2) downregulation decreases tumour cell growth in multiple myeloma through inhibition of NFKappa B pathway and proteasome activity. (2013)
  • Author(s): Gatt ME, Takada K, Mani M, Lerner M, Pick M, Hideshima T, Carrasco DE, Protopopov A, Ivanova E, Sangfelt O, Grander D, Barlogie B, Shaughessy JD Jr, Anderson KC, Carrasco DR
  • Journal Title: Br J Haematol Volume: 162 Issue: 2 Pages: 210-220
  • DOI: 10.1111/bjh.12365
  • Peer Reviewed
• [Journal Article] A phase II study of neoadjuvant combination chemotherapy with docetaxel, cisplatin, and S-1 for locally advanced resectable gastric cancer: nucleotide excision repair (NER) as potential chemoresistance marker. (2013)
  • Author(s): Hirakawa M, Sato Y, Ohnuma H, Takayama T, Sagawa T, Nobuoka T, Harada K, Miyamoto H, Sato Y, Takahashi Y, Katsuki S, Hirayama M, Takahashi M, Ono M, Maeda M, Takada K, Hayashi T, Sato T, Miyanishi K, Takimoto R, Kobune M, Hirata K, Kato J
  • Journal Title: Cancer Chemother Pharmacol Volume: 71 Issue: 3 Pages: 789-797
  • DOI: 10.1007/s00280-013-2073-5
  • Peer Reviewed
• [Journal Article] RFP2 downregulation decreases tumor cell growth in multiple myeloma through inhibition of NF Kappa B pathway and proteasome activity (2013)
  • Author(s): Gatt ME
  • Journal Title: British Journal of Haematology Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Targeted Disruption of the BCL9/・-catenin Complex Inhibits Oncogenic Wnt Signaling. (2012)
  • Author(s): Takada K, Zhu D, Bird GH, Sukhdeo K, Zhao JJ, Mani M, Lemieux M, Carrasco DE, Ryan J, Horst D, Fulcinti M, Munshi NC, Xu W, Kung AL, Shivdasani RA, Walensky LD, Carrasco DR
  • Journal Title: Sci Transl Med Volume: 4(148) Issue: 148 Pages: 148-117
  • DOI: 10.1126/scitranslmed.3003808
  • Peer Reviewed
• [Journal Article] Diagnostic validity of CT gastrography versus gastroscopy for primary lesions in gastric cancer: evaluating the response to chemotherapy, a retrospective analysis. (2012)
  • Author(s): Takahashi S, Hirayama M, Kuroiwa G, Kawano Y, Takada K, Sato T, Miyanishi K, Sato Y, Takimoto R, Kobune M, Kato J.
  • Journal Title: Gatric Cancer
  • Peer Reviewed
• [Journal Article] Stromal cells expressing hedgehog-interacting protein regulate the proliferation of myeloid neoplasms. (2012)
  • Author(s): Kobune M, Iyama S, Kikuchi S, Horiguchi H, Sato T, Murase K, Kawano Y, Takada K, Ono K, Kamihara Y, Hayashi T, Miyanishi K, Sato Y, Takimoto R, Kato J.
  • Journal Title: Blood Cancer J Volume: 2 Issue: 9 Pages: e87-e87
  • DOI: 10.1038/bcj.2012.36
  • Peer Reviewed
• [Journal Article] UGT1A1*28 and *6polymorphisms and nilotinib-induced unconjugated hyperbilirubinemia in a Japanese patient with chronic myelogenous leukemia. (2012)
  • Author(s): Takada K, Sato T, Iyama S, Ono K, Kamihara Y, Murase K, Kawano Y, Hayashi T, Miyanishi K, Sato Y, Kobune M, Takimoto R, Kato J
  • Journal Title: Int Canc Conf J201 Volume: 1 Pages: 220-223
  • Peer Reviewed
• [Journal Article] Targeting anticancer drug delivery to pancreatic cancer cells using a fucose-bound nanoparticle approach. (2012)
  • Author(s): Yoshida M, Takimoto R, Murase K, Sato Y, Hirakawa M, Tamura F, Sato T, Iyama S, Osuga T, Miyanishi K, Takada K, Hayashi T, Kobune M, Kato J.
  • Journal Title: PLoS One Volume: 7(7) Issue: 7 Pages: e39545-e39545
  • DOI: 10.1371/journal.pone.0039545
  • Peer Reviewed
• [Journal Article] Successful treatment bu fibrin glue sealant for pneumothorax with chronic GVHD resistant to autologous blood patch pleurodesis. (2012)
  • Author(s): Iyama S, Sato T, Murase K, Kikuchi S, Kamihara Y, Ono K, Takada K, Miyanishi K, Sato Y, Takimoto R, Kobune M, Obama T, Miyajima M, Watanabe A, Higami T, Hirayama Y, Kato J.
  • Journal Title: Intern Med Volume: 51(15) Pages: 2011-2014
  • Peer Reviewed
• [Journal Article] Intermittent administration ofrecombinant human soluble thrombomodulin successfully controlled chronic disseminated intravascular coagulation in a patient with dissecting aortic aneurysm on an outpatient basis. (2012)
  • Author(s): Iyama S, Sato T, et al.
  • Journal Title: Blood Coagul Fibrinolysis. Volume: 23 Issue: 6 Pages: 548-50
  • DOI: 10.1097/mbc.0b013e32835510d6
  • Peer Reviewed
• [Journal Article] Improvement of iron-mediated oxidative DNA damage in patients with transfusion-dependent myelodysplastic syndrome by treatment with deferasirox. (2012)
  • Author(s): Kikuchi S, Kobune M, Iyama S, Sato T, Murase K, Kawano Y, Takada K, Ono K, Kaneko Y, Miyanishi K, Sato Y, Hayashi T, Takimoto R, Kato J.
  • Journal Title: Free Radic Biol Med Volume: 23(6) Issue: 4 Pages: 548-550
  • DOI: 10.1016/j.freeradbiomed.2012.06.006
  • Peer Reviewed
• [Journal Article] catenin is dramatically stored and cleared in multiple myeloma by the proteasome-aggresome-autophagosome-lysosome pathway. (2012)
  • Author(s): Sukhdeo K, Mani M, Hideshima T, Takada K, Pena-Cruz V, Mendez G, Ito S, Anderson KC, Carrasco DR
  • Journal Title: Leukemia Volume: 26(5) Issue: 5 Pages: 1116-1119
  • DOI: 10.1038/leu.2011.303
  • Peer Reviewed
• [Journal Article] Prognostic significance of serum-ferritin level at diagnosis in myelodysplastic syndrome (2012)
  • Author(s): Kobune M, et al. 2^<nd>
  • Journal Title: Int J Hematol Volume: (In press) Issue: 5 Pages: 527-534
  • DOI: 10.1007/s12185-012-1048-3
  • NAID: 10030633185
  • Peer Reviewed
• [Journal Article] Prognostic significance of serum ferritin level at diagnosis in myelodysplastic syndrome (2012)
  • Author(s): Kikuchi S, Takada K, Kato J, et al
  • Journal Title: Int J Hematol Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Novel missense mutation in the TMPRSS6 gene in a Japanese female with iron-refractory iron deficiency anemia (2011)
  • Author(s): Sato T, Takimoto R, Kato J
  • Journal Title: Int J Hematol Volume: 94 Issue: 1 Pages: 101-103
  • DOI: 10.1007/s12185-011-0881-0
  • NAID: 10029536603
  • Peer Reviewed
• [Journal Article] Establishment of a simple test for iron absorption from the gastrointestinal tract (2011)
  • Author(s): Kobune M, Takimoto R, Kato, J
  • Journal Title: Int J Hematol Volume: 93 Issue: 6 Pages: 715-719
  • DOI: 10.1007/s12185-011-0878-8
  • NAID: 10029535427
  • Peer Reviewed
• [Journal Article] b-catenin is dramatically stored and cleared in multiple myeloma by the proteasome-aggresome-autophagosome-lysosome pathway (2011)
  • Author(s): Suhhdeo K, Takada K, Carrasco DR, et al
  • Journal Title: Leukemia Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Iron chelator deferasirox rescued mice from Fas-induced fulminant hepatitis (2011)
  • Author(s): Sato T, Takada K, Kato J, et al
  • Journal Title: Hepatol Res Volume: 41 Pages: 660-667
  • Peer Reviewed
• [Journal Article] Novel missense mutation in the TMPRSS6 gene in a Japanese female with iron-refractory deficiency anemia (2011)
  • Author(s): Sato T, Takada K, Kato J, et al
  • Journal Title: Int J Hematol Volume: 94 Pages: 101-103
  • Peer Reviewed
• [Journal Article] Establishment of a simple test for iron absorption from the gastrointestinal tract (2011)
  • Author(s): Kobune M, Takada K, Kato J, et al
  • Journal Title: Int J Hematol Volume: 93 Pages: 715-719
  • Peer Reviewed
• [Presentation] BCL9/beta-catenin 転写複合体を標的とした新規大腸癌治療法の開発 (2012)
  • Author(s): 高田弘一
  • Organizer: 第21回日本がん転移学会学術集会・総会
  • Place of Presentation: 広島
• [Presentation] BCL9/β-catenin 転写複合体を標的とした新規大腸癌治療法の開発 (2012)
  • Author(s): 高田弘一
  • Organizer: 第21回日本がん転移学会学術集会・総会
  • Place of Presentation: 広島
• [Presentation] BCL9は大腸癌および多発性骨髄腫において細胞増殖,浸潤・転移能および腫瘍血管新生を亢進させる (2011)
  • Author(s): 高田弘一, 加藤淳二, Carrasco DR
  • Organizer: 第91回北海道医学大会腫瘍系分科会
  • Place of Presentation: 札幌医科大学
  • Year and Date: 2011-09-17
• [Book] 分子生物学が可能とした個別化医療 (2012)
  • Author(s): 高田弘一