التفاصيل البيبلوغرافية
| العنوان: |
Impact of loss-of-function mutations at the RNF43 locus on colorectal cancer development and progression |
| المؤلفون: |
Masaaki Iwatsuki, Yukiharu Hiyoshi, Takatsugu Ishimoto, Kimi Araki, Yuki Kiyozumi, Shinichi Kanno, Hideo Baba, Toru Furukawa, Naoya Yoshida, Hidetaka Sugihara, Masaki Ohmuraya, Yuji Miyamoto, Daisuke Izumi, Tsugio Eto, Lingfeng Fu, Katsuhiko Nosho, Yoshifumi Baba, Keisuke Miyake, Yu Imamura, Hiroshi Sawayama, Kota Arima |
| المصدر: |
The Journal of Pathology. 245:445-455 |
| بيانات النشر: |
Wiley, 2018. |
| سنة النشر: |
2018 |
| مصطلحات موضوعية: |
0301 basic medicine, biology, Colorectal cancer, Azoxymethane, business.industry, medicine.disease, Pathology and Forensic Medicine, Ubiquitin ligase, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, 030220 oncology & carcinogenesis, Colorectal Polyp, Knockout mouse, Mutation testing, medicine, biology.protein, Cancer research, Gene silencing, business, Loss function |
| الوصف: |
RNF43 mutations are frequently detected in colorectal cancer cells and lead to a loss of function of the ubiquitin E3 ligase. Here, we investigated 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. Mutation analysis of the RNF43 gene locus with pyrosequencing technology detected RNF43 hotspot mutations in one (0.88%) of 113 colorectal polyp cases and in 30 (6.45%) of 465 colorectal cancer cases. Moreover, patients with colorectal cancer harbouring mutated RNF43 experienced a higher recurrence rate than those harbouring non-mutated RNF43. In addition, the growth of RNF43 wild-type colorectal cancer cell lines was significantly increased by RNF43 silencing. We generated Rnf43 knockout mice in a C57BL/6 N background by using the CRISPR-Cas9 system. Although intestinal organoids from Rnf43 knockout mice did not show continuous growth in the absence of R-spondin, 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. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| تدمد: |
0022-3417 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_________::4a7e199a097eb7b39d1deda4177a464c
https://doi.org/10.1002/path.5098 |
| حقوق: |
CLOSED |
| رقم الأكسشن: |
edsair.doi...........4a7e199a097eb7b39d1deda4177a464c |
| قاعدة البيانات: |
OpenAIRE |
