To identify the molecular mechanism underlying colorectal cancer progression via RNF43
Project/Area Number |
17K10639
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Digestive surgery
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Research Institution | Kumamoto University |
Principal Investigator |
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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)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 大腸癌 / Wntシグナル / RNF43 / RNF43遺伝子 / Wnt シグナル |
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.
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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。
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Report
(4 results)
Research Products
(8 results)
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[Journal Article] Impact of loss-of-function mutations at the RNF43 locus on colorectal cancer development and progression2018
Author(s)
Eto T, Miyake K, Nosho K, Ohmuraya M, Imamura Y, Arima K, Kanno S, Fu L, Kiyozumi Y, Izumi D, Sugihara H, Hiyoshi Y, Miyamoto Y, Sawayama H, Iwatsuki M, Baba Y, Yoshida N, Furukawa T, Araki K, Baba H, Ishimoto T
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Journal Title
The Journal of Pathology
Volume: 245
Issue: 4
Pages: 445-455
DOI
Related Report
Peer Reviewed
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[Journal Article] Activation of Transforming Growth Factor Beta 1 Signaling in Gastric Cancer-associated Fibroblasts Increases Their Motility, via Expression of Rhomboid 5 Homolog 2, and Ability to Induce Invasiveness of Gastric Cancer Cells.2017
Author(s)
Ishimoto T, Miyake K, Nandi T, Yashiro M, Onishi N, Huang KK, Joyce LN, Kalpana R, Tay ST, Suzuki Y, Cho BC, Kuroda D, Arima K, Izumi D, Iwatsuki M, Baba Y, Oki E, Watanabe M, Saya H, Hirakawa K, Baba H, Tan P.
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Journal Title
Gastroenterology
Volume: in press
Issue: 1
Pages: 191-204
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Functional role of Ring Finger Protein 43 in intestinal stem cells during colorectal tumorigenesis2017
Author(s)
Eto T, Ishimoto T, Oda E, Kuroda D, Arima K, Ohuchi M, Nakamura K, Sawayama H, Kinoshita K, Iwatsuki M, Baba Y, Sakamoto Y, Yoshida N, Baba H.
Organizer
AACR Annual Meeting 2017
Related Report
Int'l Joint Research
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