Studies for tumor suppression induced by over expression of the reprogramming factors.

• Project/Area Number: 16K10161
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kochi University
• Principal Investigator: TAKAISHI Mikiro 高知大学, 教育研究部医療学系臨床医学部門, 助教 (10303223)
• Co-Investigator(Kenkyū-buntansha): 佐野 栄紀 高知大学, 教育研究部医療学系臨床医学部門, 教授 (80273621)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: がん抑制 / 悪性黒色腫 / 間葉－上皮移行 / メラノーマ / 間葉ー上皮移行 / 再プログラミング因子 / 癌

Outline of Final Research Achievements

Over expression of reprogramming factors (OCT4, SOX2, KLF4, c-MYC, and LIN28) induced mesenchymal-epithelial transition (MET) like trans-differentiation in melanoma cells. The reprogramming factors introduced cells changed their morphology to epithelial, and expression of melanocyte specific genes and EMT-related genes was suppressed in the cells. Tumorigenicity in lungs after the cell inoculation via tail vein was obviously attenuated. Dephosphorylation of MEK, ERK, and AKT, and increased PP2A were observed in the cells.

Academic Significance and Societal Importance of the Research Achievements

悪性黒色腫細胞に再プログラミング因子を導入することによりMET様の形質転換と悪性度の減弱化が生じることを示した。これにはPP2A増加によるRAF-MEK-ERKおよびPI3K-AKTシグナル伝達経路の抑制が関わることが示唆された。これらの発見が新たながん治療につながることを期待する。

Research Products

• [Journal Article] Transdifferentiation of Melanoma Cells by the Reprogramming Factors Attenuates Malignant Nature In?Vitro and In?Vivo (2019)
  • Author(s): Takaishi Mikiro、Sano Shigetoshi
  • Journal Title: Journal of Investigative Dermatology Volume: 139 Issue: 1 Pages: 254-257
  • DOI: 10.1016/j.jid.2018.06.179
  • Peer Reviewed
• [Presentation] Forced expression of the reprogramming factors leads to attenuation of melanoma malignancy through MET-like transdifferentiation and suppression of MAPK and AKT pathways (2018)
  • Author(s): Mikiro Takaishi and Shigetoshi Sano
  • Organizer: International Investigative Dermatology 2018
  • Int'l Joint Research
• [Presentation] 再プログラミング因子による分化転換は悪性黒色腫細胞の悪性度を減少させる。 (2018)
  • Author(s): 高石樹朗、佐野栄紀
  • Organizer: 第４１回日本分子生物学会年会
• [Presentation] Forced expression of the reprogramming factors attenuated the malignant nature of melanoma cells. (2017)
  • Author(s): Mikiro Takaishi, Shigetoshi Sano
  • Organizer: European Society for Dermatological Research
  • Int'l Joint Research