Studied on the mechanisms of cancer metastasis and proliferation regulated by a new molecule

• Project/Area Number: 15K20372
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional basic dentistry
• Research Institution: Hiroshima University
• Principal Investigator: Asano Satoshi 広島大学, 医歯薬保健学研究院(歯), 助教 (30570535)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 乳癌細胞 / 転移 / 細胞移動 / イノシトールリン脂質 / PI3-kinase / 細胞増殖 / 乳腺癌細胞

Outline of Final Research Achievements

Lamellipodia are formed at the leading edge of migrating cells, and the formation is regulated by the metabolism of PI(4,5)P2, an inositol phospholipid, into PI(3,4,5)P3. Phospholipase C (PLC)-related but catalytically inactive protein (PRIP) has high homology to PLC-δ1 and binds to PI(4,5)P2 at the pleckstrin homology (PH) domain. However, the functions of PRIP in the regulation of phosphoinositide signaling have not been determined.
In this study, we examined the potential role and mechanisms of PRIP in controlling phosphoinositide metabolism and migration activity of cancer cells. PRIP overexpression in MCF-7 and BT-549 human breast cancer cells inhibited cell migration in vitro and metastasis development in vivo. PI(3,4,5)P3 production was decreased in Prip-overexpressing MCF-7 and BT-549 cells. Collectively, the suppressor activity of PRIP in PI(4,5)P2 metabolism regulates the tumour migration, suggesting PRIP as a promising target for protection against metastatic progression.

Research Products

• [Journal Article] General anesthetic actions on GABAA receptors in vivo are reduced in phospholipase C-related catalytically inactive protein knockout mice. (2017)
  • Author(s): Hayashiuchi M, Kitayama T, Morita K, Yamawaki Y, Oue K, Yoshinaka T, Asano S, Harada K, Kang Y, Hirata M, Irifune M, Okada M, Kanematsu T.
  • Journal Title: Journal of Anesthesia Volume: in press Issue: 4 Pages: 531-538
  • DOI: 10.1007/s00540-017-2350-2
  • Peer Reviewed / Open Access
• [Journal Article] Phospholipase C-related catalytically inactive protein-knockout mice display increased induction of uncoupling protein 1 in adipose tissues following chronic cold exposure. (2017)
  • Author(s): Kana Oue, Yosuke Yamawaki, Satoshi Asano, Mizokami Akiko, Masato Hirata, Masahiro Irifune, Takashi Kanematsu.
  • Journal Title: Journal of Oral Biosciences Volume: 印刷中 Issue: 2 Pages: 108-112
  • DOI: 10.1016/j.job.2017.04.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Phospholipase C-related catalytically inactive protein is a new modulator of thermogenesis promoted by β-adrenergic receptors in brown adipocytes (2015)
  • Author(s): Kana Oue, Jun Zhang, Kae Harada-Hada, Satoshi Asano, Yosuke Yamawaki, Masaki Hayashiuchi, Hisako Furusho, Takashi Takata, Masahiro Irifune, Masato Hirata, Takashi Kanematsu
  • Journal Title: Journal of Biological Chemistry Volume: 291 Issue: 8 Pages: 4185-96
  • DOI: 10.1074/jbc.m115.705723
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Expression of phospholipase C-related catalytically inactive protein suppresses cancerous metastasis (2017)
  • Author(s): 浅野智志、兼松隆
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎ブリックホール（長崎県・長崎市）
  • Year and Date: 2017-03-15
• [Presentation] Tumor cell migration is regulated by PRIP-mediated phosphatidylinositol turnover (2016)
  • Author(s): 浅野智志、兼松隆
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-03-09
• [Presentation] Suppression of PI3K-dependent breast cancer cell migration by PRIP (2016)
  • Author(s): 浅野智志、兼松隆
  • Organizer: GAP (Global Academic Program) related meeting
  • Place of Presentation: 広島大学（広島県・広島市）
  • Int'l Joint Research
• [Presentation] Suppression of breast cancer cell migration by PRIP, an upstream regulator of phosphoinositide 3-kinase signaling pathway (2015)
  • Author(s): 浅野智志、兼松隆
  • Organizer: 第48回広島大学歯学会総会
  • Place of Presentation: 広島大学（広島県・広島市）
  • Year and Date: 2015-06-27
• [Presentation] PRIP分子による細胞移動の調節PRIPは細胞膜におけるPI(3,4,5)P3合成を調節している (2015)
  • Author(s): 浅野智志、兼松隆
  • Organizer: 第56回日本生化学会中国・四国支部例会
  • Place of Presentation: 島根大学（島根県・松江市）
  • Year and Date: 2015-05-29