The identification of functional role of CD44 in redox status and the application to therapeutic strategy in cancer

• Project/Area Number: 24591912
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Kumamoto University
• Principal Investigator: ISHIMOTO takatsugu 熊本大学, 医学部附属病院, 非常勤診療医師 (00594889)
• Co-Investigator(Kenkyū-buntansha): IWATSUKI Masaaki 熊本大学, 医学部附属病院, 非常勤診療医師 (50452777) ; BEPPU Toru 熊本大学, 医学部附属病院, 特任教授 (70301372)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: CD44 / xCT / microRNA / CTC / 消化器癌 / 癌幹細胞 / 活性酸素 / 治療抵抗性

Outline of Final Research Achievements

CD44v-xCT plays a key role in the maintenance of undifferentiated head and neck squamous cell carcinoma (HNSCC) tumors rather than differentiated-type HNSCC tumors, and confers the ability of evasion from oxidative stress in several types of cancer and thereby promotes the lung metastasis. Furthermore, microRNA qRT-PCR array analysis identified miR-328 as one of the microRNAs targeting CD44 in gastric cancer. miR-328-CD44 signaling mediated by chronic inflammation is implicated in gastric cancer development and progression.

Research Products

• [Journal Article] Macrophage-derived reactive oxygen species suppress miR-328 targeting CD44 in cancer cells and promote redox adaptation (2014)
  • Author(s): Ishimoto T, Sugihara H, Watanabe M, Sawayama H, Iwatsuki M, Baba Y, Okabe H, Hidaka K, Yokoyama N, Miyake K, Yoshikawa M, Nagano O, Komohara Y, Takeya M, Saya H, Baba H.
  • Journal Title: Carcinogenesis Volume: 35(5) Issue: 5 Pages: 1003-11
  • DOI: 10.1093/carcin/bgt402
  • Peer Reviewed / Open Access
• [Journal Article] Functional role of CD44v-xCT system in the development of spasmolytic polypeptide-expressing metaplasia (2013)
  • Author(s): Wada T, Ishimoto T, Seishima R, Tsuchihashi K, Yoshikawa M, et al
  • Journal Title: Cancer Science Volume: 104 Issue: 10 Pages: 1323-9
  • DOI: 10.1111/cas.12236
  • Peer Reviewed
• [Journal Article] xCT Inhibition Depletes CD44v-Expressing Tumor Cells That Are Resistant to EGFR-Targeted Therapy in Head and Neck Squamous Cell Carcinoma (2013)
  • Author(s): Yoshikawa M, Tsuchihashi K, Ishimoto T, Yae T, Motohara T, Sugihara E, Onishi N, Masuko T, Yoshizawa K, Kawashiri S, Mukai M, Asoda S, Kawana H, Nakagawa T, Saya H, Nagano O
  • Journal Title: Cancer Res Volume: 73(6) Issue: 6 Pages: 1855-1866
  • DOI: 10.1158/0008-5472.can-12-3609-t
  • Peer Reviewed
• [Journal Article] Kinoshita H, Okabe H, Beppu T,Chikamoto A, Hayashi H, Imai K, MimaK, Nakagawa S, Ishimoto T, Miyake K,Yokoyama N, Ishiko T, Baba (2012)
  • Author(s): Kinoshita H, Okabe H, Beppu T,Chikamoto A, Hayashi H, Imai K, MimaK, Nakagawa S, Ishimoto T, Miyake K,Yokoyama N, Ishiko T, Baba
  • Journal Title: Oncol Rep Volume: 29 Issue: 2 Pages: 685-9
  • DOI: 10.3892/or.2012.2162
  • Peer Reviewed
• [Journal Article] Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell. (2012)
  • Author(s): Yae T, Tsuchihashi K, Ishimoto T, Motohara T, Yoshikawa M, Yoshida GJ, Wada T, Masuko T,Mogushi K, Tanaka H, Osawa T, Kanki Y, et al
  • Journal Title: Nature Communications Volume: 6;3 Issue: 1 Pages: 883-883
  • DOI: 10.1038/ncomms1892
  • Peer Reviewed
• [Presentation] Macrophage-derived reactive oxygen species suppress miR-328 targeting CD44 in gastrointestinal cancer cells and promote redox adaptation (2014)
  • Author(s): Ishimoto T
  • Organizer: AACR Annual Meeting 2014
  • Place of Presentation: San Diego, California
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] 消化器癌におけるCD44発現制御機構を標的とした治療戦略 (2014)
  • Author(s): 石本 崇胤
  • Organizer: 第114回日本外科学会定期学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-04-03 – 2014-04-05
• [Presentation] Macrophage-derived reactive oxygen species suppress miR-328 targeting CD44 in gastrointestinal cancer cells and promote redox adaptation (2013)
  • Author(s): 石本 崇胤
  • Organizer: AACR Annual Meeting 2013
  • Place of Presentation: ワシントン
• [Presentation] 消化器癌幹細胞におけるCD44の機能的役割と発現制御 (2013)
  • Author(s): 石本 崇胤
  • Organizer: 第113回日本外科学会
  • Place of Presentation: マリンメッセ福岡
• [Presentation] CD44 expression via miR-328 suppression in Helicobacter pylori infected gastric mucosa causes cancer initiation and progression (2013)
  • Author(s): 石本 崇胤
  • Organizer: 国際胃がん学会(IGCC) 2013
  • Place of Presentation: イタリア・ベローナ
• [Presentation] 消化器癌において癌幹細胞マーカーを制御するmicroRNAの同定と機能解析 (2013)
  • Author(s): 石本 崇胤
  • Organizer: 第68回日本消化器外科学会
  • Place of Presentation: 宮崎・シーガイヤコンベンションセンター
• [Presentation] 消化器癌におけるmicroRNAを介したCD44発現制御の解明 (2013)
  • Author(s): 石本 崇胤
  • Organizer: 第51回日本癌治療学会学術集会
  • Place of Presentation: 国立京都国際会館
• [Presentation] 治療抵抗性がん癌幹細胞に対する新しい治療戦略 (2012)
  • Author(s): 石本 崇胤
  • Organizer: 第112回日本外科学会定期学術集会
  • Place of Presentation: 幕張メッセ国際会議場
• [Presentation] 腫瘍微小環境における癌幹細胞マーカーの発現制御 (2012)
  • Author(s): 石本 崇胤
  • Organizer: 第67回日本消化器外科学会
  • Place of Presentation: 富山県民会館
• [Presentation] 消化器癌における酸化ストレス抵抗性を獲得する分子メカニズム (2012)
  • Author(s): 石本 崇胤
  • Organizer: 2012年度日本消化器関連学会週間（JDDW 2012）
  • Place of Presentation: 神戸国際展示場
• [Presentation] 消化器癌における癌幹細胞マーカー発現制御機構の解明 (2012)
  • Author(s): 石本 崇胤
  • Organizer: 第23回日本消化器癌発生学会
  • Place of Presentation: 徳島県鳴門市ルネッサンスリゾートナルト