5-FU resistance mechanism between hematopoietic stem cells and colon cancer stem cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670376
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: National Cancer Center Japan
• Principal Investigator: YASUNAGA Masahiro 独立行政法人国立がん研究センター, その他部局等, ユニット長 (80450576)
• Research Collaborator: MATSUMURA Yasuhiro 国立がん研究センター、臨床開発センター, 新薬開発分野, 分野長 (90209619)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 大腸がん / SLC6A6 / ５－ＦＵ / 抗がん剤耐性 / がん幹細胞 / 造血幹細胞 / トランスポーター / バイオインフォマティクス

Outline of Final Research Achievements

SLC6A6-knock down colon cancer (CC) cells showed increased chemosensitivity 5-100 fold. Moreover, in the cells, many genes specific to hematopoietic stem cell (HSC) were decreased. Comprehensive　analysis to find the regulatory molecules of the chemoresistance common between HSCs and CC cells was conducted. 1.ATG-gene, 2. FOX-related transcription factor, 3. Integrin-Src or 4. regulator of glucose metabolism were selected. The functional analysis indicated that ATG-gene was strongly associated with the survival of the side population cells and the chemosensitivity in colon cancer cells. We found that it was novel autophagic signaling pathway.

Free Research Field

腫瘍学