To identify the molecular mechanism underlying colorectal cancer progression via RNF43

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10639
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: Hdetaka Sugihara 熊本大学, 病院, 非常勤診療医師 (10608863)
• Co-Investigator(Kenkyū-buntansha): 石本 崇胤 熊本大学, 病院, 特任准教授 (00594889) ; 今井 克憲 熊本大学, 大学院生命科学研究部(医), 助教 (60555746) ; 今村 裕 公益財団法人がん研究会, 有明病院 消化器外科, 医長 (70583045)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 大腸癌 / Wntシグナル / RNF43

Outline of Final Research Achievements

We identified the clinical significance of RNF43 mutations in a large Japanese cohort and the role of RNF43 at various stages of colorectal cancer development and progression. Patients with colorectal cancer harbouring mutated RNF43 experienced a higher recurrence rate than those harbouring non-mutated RNF43. We generated Rnf43 knockout mice. An azoxymethane/dextran sodium sulphate mouse model demonstrated that tumours were markedly larger in Rnf43 knockout mice than in wild-type mice.
These findings provide evidence that Wnt signalling activation by RNF43 mutations during the tumourigenic stage enhances tumour growth and promotes a high recurrence rate in colorectal cancer patients.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

本研究ではRNF43 knockout マウスを用いて消化管上皮および大腸腫瘍進展における RNF43発現意義を明らかにしてきた。
大腸 癌においてAPCやβ-cateninのmutationを介した増殖・進展機構に関する報告は数多く認める が、RNF43のmutationや発現低下が腫瘍増大・進展に与える影響について明らかにすることは学術的意義の大きいところといえる。