Analyses of molecular mechanism of the glycan-dependent adaptation of tumor cells to tumor microenvironments

• Project/Area Number: 26430118
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kumamoto University
• Principal Investigator: Ohtsubo Kazuaki 熊本大学, 大学院生命科学研究部(保), 教授 (30525457)
• Co-Investigator(Renkei-kenkyūsha): KOREKANE Hiroaki 独立行政法人理化学研究所, 疾患糖鎖研究チーム, 研究員 (50421912) ; NAKAJIMA Kazuki 独立行政法人理化学研究所, 新液播く機能研究チーム, 研究員 (10442998)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 糖鎖修飾 / がん糖鎖 / シアリルTn抗原 / 転移 / 浸潤 / 低酸素 / 糖鎖 / sTn抗原 / がん転移 / がん微小環境 / 糖転移酵素 / 抗アポトーシス

Outline of Final Research Achievements

We analyzed molecular mechanisms of the Sialyl-Tn (sTn) antigen-induced alterations encompassing the reduced cell proliferation, the acquisition of anti-oxidative stress and anti-apoptosis under hypoxic conditions which are based on the tumor adaptation to dramatically changing microenvironments, and then we found that sTn antigen reduces cell cycle and induces antioxidant enzymes that confers anti-apoptotic functions on tumor cells under hypoxic conditions. These sTn antigen-induced cellular functions are important for survival and metastasis of tumor cells.

Research Products

• [Journal Article] Influence of SIGLEC9 polymorphisms on COPD phenotypes including exacerbation frequency. (2017)
  • Author(s): Ishii T, Angata T, Wan ES, Cho MH, Motegi T, Gao C, Ohtsubo K, Kitazume S, Gemma A, Pare PD, Lomas DA, Silverman EK, Taniguchi N, Kida K
  • Journal Title: Respirology Volume: 22 Issue: 4 Pages: 684-690
  • DOI: 10.1111/resp.12952
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A keratan sulfate disaccharide prevents inflammation and the progression of emphysema in murine models. (2017)
  • Author(s): Gao C, Fujinawa R, Yoshida T, Ueno M, Ota F, Kizuka Y, Hirayama T, Korekane H, Kitazume S, Maeno T, Ohtsubo K, Yoshida K, Yamaguchi Y, Lepenies B, Aretz J, Rademacher C, Kabata H, Hegab AE, Seeberger PH, Betsuyaku T, Kida K, Taniguchi N.
  • Journal Title: American Journal of Physiology Lung Cellular and Molecular Physiology Volume: 312 Issue: 2 Pages: L268-L276
  • DOI: 10.1152/ajplung.00151.2016
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Disease-associated glycans on cell surface proteins. (2016)
  • Author(s): Takahashi M, Kizuka Y, Ohtsubo K, Gu J, Taniguchi N.
  • Journal Title: Molecular Aspects of Medicine Volume: 51 Pages: 56-70
  • DOI: 10.1016/j.mam.2016.04.008
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Glyco-redox, a link between oxidative stress and changes of glycans: Lessons from research on glutathione, reactive oxygen and nitrogen species to glycobiology. (2016)
  • Author(s): N. Taniguchi, Y. Kizuka, S. Takamatsu, E. Miyoshi, C. Gao, K. Suzuki, S. Kitazume, K. Ohtsubo
  • Journal Title: Arch. Biochem. Biphys. Volume: 595 Pages: 72-80
  • DOI: 10.1016/j.abb.2015.11.024
  • Peer Reviewed / Open Access
• [Journal Article] Loss of α1,6-fucosyltransferase inhibits chemical-induced hepatocellular carcinoma and tumorigenesis by down-regulating several cell signaling pathways
  • Author(s): Yuqin Wang, Tomohiko Fukuda, Tomoya Isaji, Jishun Lu, Sanghun Im, Qinglei Hang, Wei Gu, Sicong Hou, Kazuaki Ohtsubo, Jianguo Gu
  • Journal Title: The FASEB Journal Volume: 29 Issue: 8 Pages: 3217-3227
  • DOI: 10.1096/fj.15-270710
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 膵臓β細胞膜におけるN型糖鎖を介した栄養センサー分子の局在制御 (2016)
  • Author(s): 前田賢人, 田崎雅義, 安東由喜雄, 大坪和明
  • Organizer: 第８９回日本生化学会大会
  • Place of Presentation: 仙台国際センター／東北大学川内北キャンパス
• [Presentation] Sialyl-Tn抗原発現による酸化ストレス耐性獲得メカニズム (2016)
  • Author(s): 田嶋彩香, 高宮里奈, 前田賢人, 藤井柊作, 大坪和明
  • Organizer: 第８９回日本生化学会大会
  • Place of Presentation: 仙台国際センター／東北大学川内北キャンパス
• [Presentation] 糖鎖を介した低酸素環境におけるがん細胞の生存・転移戦略 (2016)
  • Author(s): 藤井柊作, 高宮里奈, 高松真二, 是金宏昭, 前田賢人, 田嶋彩香, 谷口直之, 大坪和明
  • Organizer: 第８９回日本生化学会大会
  • Place of Presentation: 仙台国際センター／東北大学川内北キャンパス
• [Presentation] sTn抗原合成阻害によるがん転移抑制を目的とした新規抗がん剤の探索 (2015)
  • Author(s): 藤井柊作、大坪和明、是金宏昭、斎藤臣雄
  • Organizer: BMB２０１５
  • Place of Presentation: 神戸（神戸国際会議場）
  • Year and Date: 2015-12-03
• [Presentation] 細胞環境に応じたグルコース取り込みを可能とする糖鎖修飾 (2015)
  • Author(s): 大坪和明
  • Organizer: BMB２０１５
  • Place of Presentation: 神戸（神戸国際会議場）
  • Year and Date: 2015-12-02
• [Presentation] N型糖鎖による膵臓β細胞膜のセンサードメイン形成メカニズムの解明 (2015)
  • Author(s): 前田賢人、田崎雅義、安東由喜雄、大坪和明
  • Organizer: BMB２０１５
  • Place of Presentation: 神戸（神戸国際会議場）
  • Year and Date: 2015-12-01
• [Presentation] Pharmacological targeting of ST6GalNAc-I for suppression of tumor metastasis (2015)
  • Author(s): Shusaku Fujii, Rina Takamiya, Shinji Takamatsu, Hiroaki Korekane, Kento Maeda, Naoyuki Taniguchi, Kazuaki Ohtsubo
  • Organizer: 第３４回 日本糖質学会 年会
  • Place of Presentation: 東京（東京大学）
  • Year and Date: 2015-07-30
• [Presentation] Sialyl-Tn antigen is a potential target for the development of metastasis specific anti-tumor drugs (2014)
  • Author(s): Shusaku Fujii, Rina Takamiya, Shinji Takamatsu, Hiroaki Korekane, Naoyuki Taniguchi, Kazuaki Ohtsubo
  • Organizer: 2014 Society for Glycobiology & JSCR JOINT MEETING
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 2014-11-16 – 2014-11-22
• [Book] Sugar Chains (2015)
  • Author(s): Tadashi Suzuki, Kazuaki Ohtsubo, Naoyuki Taniguchi
  • Total Pages: 288
  • Publisher: Springer
• [Remarks] 大坪和明研究室 【大学院生命科学研究部 先端生命医療科学部門 医療技術科学講座 生体情報解析学】
  • URL: http://www.kumamoto-u.ac.jp/kenkyuu/laboratory-exploration/57-2015summer