Search for new target molecules to overcome drug resistance using the Hsp72 binding protein interactome

• Project/Area Number: 24650647
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Clinical oncology
• Research Institution: Osaka City University
• Principal Investigator: TAKAHASHI KATSUYUKI 大阪市立大学, 医学(系)研究科(研究院), 薬剤部職員 (10597751)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 抗癌剤耐性 / 分子シャペロン / 熱ショックタンパク質 / プロテオミクス / シャペロン

Research Abstract

Heat shock protein 72 (Hsp72) has functions such as promotion of protein folding, stabilizing oncogenic proteins, and avoiding stress. It has reported that Hsp72 overexpressed in gastric cancer was associated with resistance to chemotherapy. We think that Hsp72 client proteins would play an important role in drug resistance.
All experiments used human gastric cancer cell line, 2M and oxaliplatin (OXA) resistant 2M (2M/OXA). We identified 22 specific Hsp72-client proteins in 2M/OXA by LC/MS/MS. One of the client proteins, stromal cell derived factor 2 siRNA enhanced OXA inducing cell death in 2M/OXA.
Hsp72-client proteins in drug-resistant cells may target molecules to overcome drug resistance.

Research Products

• [Journal Article] Hsc70 contributes to cancer cell survival by preventing Rab1A degradation under stress conditions (2014)
  • Author(s): Tanaka M, Mun S, Harada A, Ohkawa Y, Inagaki A, Sano S, Takahashi K, Izumi Y, Osada-Oka M, Wanibuchi H, Yamagata M, Yukimura T, Miura K, Shiota M, Iwao H
  • Journal Title: PLOS ONE Volume: (in press)
  • Peer Reviewed
• [Journal Article] Fibroblast growth factor-2 anchoring on plasma membrane is critical for endothelial cell survival (2014)
  • Author(s): Tanaka M, Yamaguchi M, Kawamoto Y, Takahashi K, Inagaki A, Osada-Oka M, Harada A, Wanibuchi H, Izumi Y, Miura K, Shiota M, Iwao H, Ohkawa Y
  • Journal Title: Monoclon Antib Immunodiagn Immunother Volume: (in press)
  • Peer Reviewed
• [Journal Article] Fibroblast growth factor-2 anchoring on plasma membrane is critical for endothelial cell survival (2014)
  • Author(s): Tanaka M, Yamaguchi M, Kawamoto Y, Takahashi K, Inagaki A, Osada-Oka M, Harada A, Wanibuchi H, Izumi Y, Miura K, Shiota M, Iwao H, Ohkawa Y.
  • Journal Title: Monoclon Antib Immunodiagn Immunother Volume: in press
  • Peer Reviewed
• [Journal Article] Hsc70 contributes to cancer cell survival by preventing Rab1A degradation under stress conditions (2014)
  • Author(s): Tanaka M, Mun S, Harada A, Ohkawa Y, Inagaki A, Sano S, Takahashi K, Izumi Y, Osada-Oka M, Wanibuchi H, Yamagata M, Yukimura T, Miura K, Shiota M, Iwao H.
  • Journal Title: PLOS ONE Volume: in press
  • Peer Reviewed
• [Journal Article] Establishment of a 5-fluorouracil-resistant triple-negative breast cancer cell line (2013)
  • Author(s): Takahashi K, Tanaka M, Inagaki A, Wanibuchi H, Izumi Y, Miura K, Nagayama K, Shiota M, Iwao H.
  • Journal Title: Int J Oncol. Volume: 43 Issue: 6 Pages: 1985-91
  • DOI: 10.3892/ijo.2013.2135
  • Peer Reviewed
• [Journal Article] 高校生競技者および指導者のドーピングに対する知識・意識に関する調査研究 (2013)
  • Author(s): 高橋克之，中村安孝，南野優子，川口博資，西川武司，永山勝也，岩尾 洋
  • Journal Title: 医療薬学 Volume: 39 Pages: 166-173
  • NAID: 130004502795
  • Peer Reviewed
• [Journal Article] Tumor growth inhibitory effect of ADAMTS1 is accompanied by the inhibition of tumor angiogenesis. (2012)
  • Author(s): Obika M
  • Journal Title: Cancer Science Volume: 10 Issue: 10 Pages: 1889-1897
  • DOI: 10.1111/j.1349-7006.2012.02381.x
  • Peer Reviewed
• [Presentation] 胃癌細胞株においてHsp72はオキサリプラチン耐性の獲得に寄与する (2014)
  • Author(s): 髙橋克之
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 宮城
  • Year and Date: 2014-03-21
• [Presentation] Heat shock protein 72 is a key molecule in oxaliplatin resistance in human gastric cancer cell (2014)
  • Author(s): Katsuyuki Takahashi
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台国際センター（宮城）
• [Presentation] The search for diagnostic biomarkers of multiple myeloma by analysis of HSP72 interactome (2013)
  • Author(s): Tanaka M
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 神奈川
  • Year and Date: 2013-10-04
• [Presentation] Isolation of HSP72-binding protein in the serum (2013)
  • Author(s): Shiota M
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 神奈川
  • Year and Date: 2013-10-03
• [Presentation] Identification of drug resistance-related protein in Triple-negative breast cancer using a proteomic approach (2013)
  • Author(s): Takahashi K
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 神奈川
  • Year and Date: 2013-10-03
• [Presentation] HSC70-targeted proteomics revealed the association of RAB1A with stress response in cancer cells (2013)
  • Author(s): Tanaka M
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2013-03-21
• [Presentation] Identification of drug resistance-related protein in Triple-negative breast cancer (2013)
  • Author(s): Katsuyuki Takahashi
  • Organizer: 第72回日本癌学会学術大会
  • Place of Presentation: パシフィコ横浜（神奈川）
• [Presentation] Isolation of HSP72-binding protein in the seruｍ (2013)
  • Author(s): Masayuki Shiota
  • Organizer: 第72回日本癌学会学術大会
  • Place of Presentation: パシフィコ横浜（神奈川）
• [Presentation] The search for diagnostic biomarkers of multiple myeloma by analysis of HSP72 interactome (2013)
  • Author(s): Masako Tanaka
  • Organizer: 第72回日本癌学会学術大会
  • Place of Presentation: パシフィコ横浜（神奈川）
• [Presentation] HSC70-targeted ptoteomics revealed the association of RAB1A with stress response in cancer cell. (2013)
  • Author(s): Masako Tanaka
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡国際会議場（福岡県）
• [Presentation] 病院実務実習における臨床研究体験実習の導入と評価 (2013)
  • Author(s): 高橋克之
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] A novel neutralizing antibodies against FGF-2 induced endothelial cell death (2012)
  • Author(s): Shiota M
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 北海道
  • Year and Date: 2012-09-11
• [Presentation] Proteomic analysis of heat shock protein 72 client proteins in drug-resistant gastric cancer cell (2012)
  • Author(s): Takahashi K
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 北海道
  • Year and Date: 2012-09-09
• [Presentation] Proteomic analysis of Hsc70 client proteins targeting stress response in cancer cells (2012)
  • Author(s): Tanaka M
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 北海道
  • Year and Date: 2012-09-09
• [Presentation] 分子シャペロンHsc70を標的とした癌のストレス応答分子同定法の確立 (2012)
  • Author(s): 田中昌子
  • Organizer: 第121回日本薬理学会近畿部会
  • Place of Presentation: 徳島
  • Year and Date: 2012-06-29
• [Presentation] 分子シャペロンHsc70を標的とした癌のストレス応答分子同定法の確立 (2012)
  • Author(s): 田中昌子
  • Organizer: 第121回日本薬理学会近畿支部
  • Place of Presentation: あわぎんホール(徳島県）
• [Presentation] Proteomic analysis of heat shock protein 72 client proteins in drug-resistant gastric cancer cell. (2012)
  • Author(s): Katsuyuki Takahashi
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌（北海道）
• [Presentation] Proteomic analysis of Hsc70 client proteins targeting stress response in cancer cells. (2012)
  • Author(s): Masako Tanaka
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌（北海道）
• [Presentation] A novel neutralizing antibodies against FGF-2 induced endothelial cell death. (2012)
  • Author(s): Masayuki Shiota
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌（北海道）
• [Presentation] ワルファリンカリウムとフッ化ピリミジン系抗癌剤併用の現状と課題 (2012)
  • Author(s): 高橋克之
  • Organizer: 第22回医療薬学会年会
  • Place of Presentation: 朱鷺メッセ(新潟県）