Homeobox B9 induces EMT-associated radioresistance by accelerating DNA damage responses

• Project/Area Number: 23791499
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Keio University
• Principal Investigator: HAYASHIDA Tetsu 慶應義塾大学, 医学部, 助教 (80327543)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 乳癌 / HOXB9 / TGFβ / 放射線 / ATM / EMT / 放射線耐性

Research Abstract

We show that HOXB9 confers resistance to ionizing radiation by promoting DNA damage response. In non-irradiated cells, HOXB9 induces spontaneous DNA damage, phosphorylated histone 2AX and p53 binding protein 1 foci, and increases baseline ataxia telangiec

Research Products

• [Journal Article] Homeobox B9 induces epithelial-to-mesenchymal transition-associated radioresistance by accelerating DNA damage responses. (2012)
  • Author(s): Chiba N, Cornalis V, Shiotani B, Takahashi F, et al.
  • Journal Title: Proc Natl Acad Sci USA Volume: 109 Issue: 8 Pages: 2760-5
  • DOI: 10.1073/pnas.1018867108
  • Peer Reviewed
• [Journal Article] HOXB9 expression promoting tumor cell proliferation and angiogenesis is associated with clinical outcomes in breast cancer patients. (2012)
  • Author(s): Seki H, Hayashida T, Jinno H, Hirose S, Sakata M, Takahashi M, Maheswaran S, Mukai M, Kitagawa Y.
  • Journal Title: Ann Surg Oncol Volume: 19(6) Issue: 6 Pages: 1831-40
  • DOI: 10.1245/s10434-012-2295-5
  • Peer Reviewed
• [Journal Article] Direct inhibition of the transforming growth factor-β pathway by protein-bound polysaccharide through inactivation of Smad2 signaling (2012)
  • Author(s): Ono Y, Hayashida T, Konagai A, Okazaki H, Miyao K, Kawachi S, Tanabe M, Shinoda M, Jinno H, Hasegawa H, Kitajima M, Kitagawa Y.
  • Journal Title: Cancer Sci. Volume: 103(2) Issue: 2 Pages: 317-24
  • DOI: 10.1111/j.1349-7006.2011.02133.x
  • Peer Reviewed
• [Journal Article] Epithelial -mesenchymal transition and tumor microenvironment propose the seed and soil theory of the present age (2012)
  • Author(s): Tetsu Hayashida
  • Journal Title: Nihon Rinsho.Suppl Volume: 7 Pages: 203-7
• [Journal Article] Homeobox B9 induces epithelial-to-mesenchymal transition-associated radioresistance by accelerating DNA damage responses. (2012)
  • Author(s): Naokazu Chiba
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 109(8) Pages: 2760-5
  • Peer Reviewed
• [Journal Article] HOXB9 expression promoting tumor cell proliferation and angiogenesis is associated with clinical outcomes in breast cancer patients. (2012)
  • Author(s): Hirohito Seki
  • Journal Title: Ann Surg Oncol. Volume: 19(6) Pages: 1831-40
  • Peer Reviewed
• [Journal Article] Direct inhibition of the transforming growth factor-β pathway by protein-bound polysaccharide through inactivation of Smad2 signaling. (2012)
  • Author(s): Yoshihiro Ono
  • Journal Title: Cancer Sci. Volume: 103(2) Pages: 317-24
  • Peer Reviewed
• [Journal Article] Epithelial-mesenchymal transition and tumor microenvironment propose the seed and soil theory of the present age (2012)
  • Author(s): Tetsu Hayashida
  • Journal Title: Nihon Rinsho. Volume: Suppl 7 Pages: 203-7
• [Journal Article] Homeobox B9 induces epithelial-to-mesenchymal transition-associated radioresistance by accelerating DNA damage responses (2012)
  • Author(s): Chiba N, Comaills V, Shiotani B, Takahashi F, Shimada T, Tajima K, Winokur D, Hayashida T, Willers H, Brachtel E, Vivanco MD, Haber DA, Zou L, Maheswaran S
  • Journal Title: Proc Natl Acad Sci U S A Volume: 109 Pages: 2760-2765
  • Peer Reviewed
• [Journal Article] Cooperation of cancer stem cell properties and epithelial-mesenchymal transition in the establishment of breast cancer metastasis. (2011)
  • Author(s): Hayashida T, Jinno H, Kitagawa Y, Kitajima M
  • Journal Title: J Oncol Volume: 2011 Pages: 1-7
  • DOI: 10.1155/2011/591427
  • Peer Reviewed
• [Presentation] HomeoboxB9 is a potential surrogate marker for bevacizumab in combination with chemotherapy in colorectal cancer (2013)
  • Author(s): 林田哲
  • Organizer: AACR/JCA Joint Conference
  • Place of Presentation: 米国 Maui
  • Year and Date: 2013-02-24
• [Presentation] HomeoboxB9 is a potential surrogate marker for bevacizumab in combination with chemotherapy in colorectal cancer (2013)
  • Author(s): Tetsu Hayashida
  • Organizer: AACR/JCA Joint Conference
  • Place of Presentation: Maui, HI, USA
• [Presentation] 大腸癌におけるHOXB9発現による 腫瘍血管新生亢進とベバシズマブの効果予測の検討 (2012)
  • Author(s): 林田哲
  • Organizer: 日本癌治療学会学術集会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2012-10-25
• [Presentation] Homeobox B9: A potential surrote marker for bevacizumab in combination with chemotherapy in colorectal cancer (2012)
  • Author(s): 林田哲
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: ロイトン札幌(札幌)
  • Year and Date: 2012-09-19
• [Presentation] Homeobox B9: a potential surrogate marker for bevacizumab in combination with chemotherapy incolorectal cancer (2012)
  • Author(s): 星野好則
  • Organizer: ASCO Annual Meeting 2012
  • Place of Presentation: 米国 Chicago
  • Year and Date: 2012-06-04
• [Presentation] Homeobox B9: a potential surrogate marker for bevacizumab in combination with chemotherapy in colorectal cancer (2012)
  • Author(s): Yoshinori Hoshino
  • Organizer: ASCO Annual Meeting 2012
  • Place of Presentation: Chicago, IL, USA
• [Presentation] Homeobox B9: A potential surrote marker for bevacizumab in combination with chemotherapy in colorectal cancer (2012)
  • Author(s): Tetsu Hayashida
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 大腸癌におけるHOXB9発現による 腫瘍血管新生亢進とベバシズマブの効果予測の検討 (2012)
  • Author(s): 林田 哲
  • Organizer: 日本癌治療学会学術集会
  • Place of Presentation: 横浜
• [Presentation] HOXB9, a Gene Promoting Tumor Angiogenesis and Proliferation, Is Significantly Associated with Poor Clincal Outcomes in ER-Positive Breast Cancer Patients (2012)
  • Author(s): Hirohito Seki
  • Organizer: San Antonio Breast Cancer Symposium 2012
  • Place of Presentation: San Antonio, TX, USA
• [Presentation] HOXB9 Expression as a New Independent Prognostic Factor in Human Breast Cancer (2011)
  • Author(s): 関大仁
  • Organizer: San Antonio Breast Cancer Symposium 2011
  • Place of Presentation: 米国 San Antonio
  • Year and Date: 2011-12-06
• [Presentation] EMT・血管新生からみた新しいSeed & Soil Theoryと乳癌治療戦略 (2011)
  • Author(s): 林田哲
  • Organizer: 第19回日本乳癌学会学術総会
  • Place of Presentation: 仙台国際センター(宮城)
  • Year and Date: 2011-09-02
• [Presentation] EMT・血管新生からみたSeed & Soil Theoryと固形癌個別化治療 (2011)
  • Author(s): 林田哲
  • Organizer: 第20回日本がん転移学会学術集会・総会
  • Place of Presentation: アクトシティ浜松 コングレスセンター(静岡)
  • Year and Date: 2011-06-30
• [Presentation] The relationship of HOXB9 expression promoting tumor cell proliferation and angiogenesis to clinical outcomes of patients with breast cancer. (2011)
  • Author(s): 林田哲
  • Organizer: 2011 ASCO Annual Meeting
  • Place of Presentation: 米国 Chicago
  • Year and Date: 2011-06-06
• [Presentation] EMT・血管新生からみた新しいSeed & Soil Theoryと乳癌治療戦略 (2011)
  • Author(s): 林田哲 神野浩光 高橋麻衣子 北川雄光
  • Organizer: 第19回日本乳癌学会学術総会
  • Place of Presentation: 仙台国際センター（宮城）
• [Presentation] EMT・血管新生からみたSeed & Soil Theoryと固形癌個別化治療 (2011)
  • Author(s): 林田哲 神野浩光 高橋麻衣子 北川雄光
  • Organizer: 第20回日本がん転移学会学術集会・総会
  • Place of Presentation: アクトシティ浜松 コングレスセンター（静岡）
• [Presentation] HOXB9 Expression as a New Independent Prognostic Factor in Human Breast Cancer (2011)
  • Author(s): Seki H, Hayashida T, Jinno H, Takahashi M, Sakata M, Hirose S, Mukai M, Kitagawa Y
  • Organizer: San Antonio Breast Cancer Symposium 2012
  • Place of Presentation: 米国 San Antonio
• [Presentation] The relationship of HOXB9 expression promoting tumor cell proliferation and angiogenesis to clinical outcomes of patients with breast cancer. (2011)
  • Author(s): T. Hayashida, H. Jinno, H. Seki, M. Takahashi, M. Sakata, S. Hirose, M. Mukai, Y. Kitagawa
  • Organizer: 2011 ASCO Annual Meeting
  • Place of Presentation: 米国 Chicago