Identification of the novel niche factor implicated in cancer stem cell maintenance in tumor stroma.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H06257
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: Kumamoto University
• Principal Investigator: ISHIMOTO Takatsugu 熊本大学, 医学部附属病院, 特任准教授 (00594889)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 胃癌 / 癌関連線維芽細胞 / 腫瘍間質 / 慢性炎症 / 癌幹細胞

Outline of Final Research Achievements

Cancer stem cell (CSC) have been implicated in chemo-resistance and tumor relapse, and the stem cell-like properties are regulated by CSC niche. However, the CSC niche in solid tumor is totally unknown. In the current study, we identified RHBDF2 as a gene overexpressed in cancer associated fibroblasts (CAFs), and showed that this molecule enhances gastric cancer (GC) cell invasion through oncogenic and non-canonical TGFB1 signaling. Further analysis using specific inhibitor of RHBDF2 may lead to the inhibition of GC invasion and metastasis.

Free Research Field

腫瘍生物学、消化器外科学

Academic Significance and Societal Importance of the Research Achievements

これまで癌細胞の性質に依ると考えられていた浸潤・転移が、腫瘍微小環境に存在する線維芽細胞（CAFs）の働きによって引き起こされることを明らかにした。さらにはCAFsを用いた網羅的な遺伝子発現解析によって、胃がん細胞とCAFsの相互作用を介した浸潤・転移機構に重要な新規遺伝子（RHBDF2）を見出しており、胃癌浸潤の新たな分子メカニズムの解明に繋がった。