The mechanism of chemotherapy resistance in colon cancer stem cells and epithelial mesenchymal transition colon cancer cells

• Project/Area Number: 16H06899
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: Matsubara Junichi 京都大学, 医学研究科, 特定助教 (40782371)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: がん幹細胞 / 大腸癌 / 上皮間葉形質転換 / 抗癌剤 / 治療抵抗性 / 化学療法 / CDKN3 / 癌 / 上皮間葉転換 / 癌幹細胞

Outline of Final Research Achievements

We developed patient-derived xenograft tumor models from clinical samples of colon cancer patients. We did in vivo chemotherapy experiments using the PDX models treated with irinotecan which is one of the standard chemotherapy drugs in clinical practice of colon cancer treatment. Cancer stem cells were sorted by FACS (fluorescence activated cell sorting) and transcriptomic analysis of the sorted cells was subsequently done. Then, we have identified CDKN3 as a new mechanism of chemotherapy resistance in colon cancer cells. CDKN3 is one of the downstream targets of transcription factor E2F4 which I previously reported as a key transcription factor in the mechanism of chemotherapy resistance.

Research Products

• [Presentation] E2F4/p107 complex regulates chemotherapy resistance in human colorectal cancer stem cells (2017)
  • Author(s): Junichi Matsubara, Yong F. Li, Piero Dalerba, Debashis Sahoo, Taichi Isobe, Russ B. Altman, Michael F. Clarke
  • Organizer: AACR Annual Meeting 2017 (American Association for Cancer Research)
  • Int'l Joint Research
• [Presentation] A E2F4/p107 complex regulates LDHA in the mechanism of chemotherapy resistance in human colorectal cancer stem cells (2017)
  • Author(s): Junichi Matsubara, Yong F. Li, Piero Dalerba, Debashis Sahoo, Russ B. Altman, Michael F. Clarke
  • Organizer: 第76回 日本癌学会学術総会
  • Int'l Joint Research