Clarification of the role of magnesium homeostasis in colorectal cancer

• Project/Area Number: 26430113
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Osaka University
• Principal Investigator: Yamazaki Daisuke 大阪大学, 微生物病研究所, 准教授 (50422415)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 大腸がん / マグネシウム / カルシウムチャネル / 腸管上皮細胞 / 細胞増殖 / 発がん / 炎症 / 悪性化

Outline of Final Research Achievements

The Mg2+ transporter CNNM4 maintains cellular magnesium homeostasis through its Mg2+ extrusion activity, and intracellular Mg2+ levels are significantly increased in Cnnm4-deficient cells. An analysis using mouse models of colorectal cancers shows that depletion of Cnnm4 promotes tumorigenesis and tumor progression in intestinal tissues. These results suggest that CNNM4 suppresses intestinal tumor development through regulation of the level of intracellular magnesium.

Research Products

• [Journal Article] Renal function of cyclin M2 Mg2+ transporter maintains blood pressure. (2017)
  • Author(s): Funato Y, Yamazaki D, Miki H.
  • Journal Title: J Hypertens. Volume: 35 Issue: 3 Pages: 585-592
  • DOI: 10.1097/hjh.0000000000001211
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Complementary role of CNNM2 in sperm motility and Ca(2+) influx during capacitation. (2016)
  • Author(s): Yamazaki D, Funato Y, Miyata H, Ikawa M, Miki H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 474 Issue: 3 Pages: 441-446
  • DOI: 10.1016/j.bbrc.2016.05.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mg²⁺ Extrusion from Intestinal Epithelia by CNNM Proteins Is Essential for Gonadogenesis via AMPK-TORC1 Signaling in Caenorhabditis elegans (2016)
  • Author(s): Ishii T, Funato Y, Hashizume O, Yamazaki D, Hirata Y, Nishiwaki K, Kono N, Arai H, Miki H.
  • Journal Title: PLoS Genet. Volume: 12 Issue: 8 Pages: e1006276-e1006276
  • DOI: 10.1371/journal.pgen.1006276
  • Peer Reviewed / Open Access
• [Journal Article] The Mg2+ transporter CNNM4 regulates sperm Ca2+ homeostasis and it is essential for reproduction (2016)
  • Author(s): Daisuke Yamazaki, Haruhiko Miyata, Yosuke Funato, Yoshitaka Fujihara, Masahito Ikawa, Hiroaki Miki
  • Journal Title: Journal of Cell Science Volume: 未定 Issue: 9 Pages: 1940-1949
  • DOI: 10.1242/jcs.182220
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Membrane Protein CNNM4-Dependent Mg2+ Efflux Suppresses Tumor Progression (2014)
  • Author(s): Yosuke Funato, Daisuke Yamazaki, Shin Mizukami, Lisa Du, Kazuya Kikuchi, Hiroaki Miki
  • Journal Title: J. Clin. Invest. Volume: 124 Issue: 12 Pages: 5398-5410
  • DOI: 10.1172/jci76614
  • Peer Reviewed
• [Presentation] Mg2+トランスポーターCNNM4は大腸での発がんを抑制する (2017)
  • Author(s): 山崎大輔、長谷川綾郁、船戸洋佑、三木裕明
  • Organizer: ConBio2017
• [Presentation] 受精能獲得にはCNNMsによる細胞内Mg2+濃度の調節が重要である (2016)
  • Author(s): 山崎大輔、宮田治彦、船戸洋佑、藤原祥高、伊川正人、三木裕明
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] Role of CNNM4 in Ca2+ influx through CatSper channel during sperm capacitation (2015)
  • Author(s): Daisuke Yamazaki, Haruhiko Miyata, Yosuke Funato, Yoshitaka Fujihara, Masahito Ikawa, Hiroaki Miki
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
  • Int'l Joint Research
• [Book] レドックス疾患学 (2018)
  • Author(s): 山崎大輔、三木裕明
  • Total Pages: 276
  • Publisher: 羊土社
  • ISBN: 9784758103695