Development of intestinal tumor therapy targeting TACC3
Project/Area Number |
25640094
|
Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
Allocation Type | Multi-year Fund |
Research Field |
Tumor therapeutics
|
Research Institution | Japanese Foundation for Cancer Research |
Principal Investigator |
Yao Ryoji 公益財団法人がん研究会, その他部局等, 研究員 (80291095)
|
Project Period (FY) |
2013-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
Keywords | 消化管腫瘍 / 分子標的治療 / Apc / 消化管オルガノイド / 消化管幹細胞 / TACC3 / 細胞分裂 / APC |
Outline of Final Research Achievements |
Human colorectal cancer is often initiated by the aberrant activation of Wnt signaling, notably following adenomatous polyposis coli (Apc) inactivation. Using organoid cultures established from conditional knockout mice and in vitro gene ablation, we showed that Apc inactivation led to aberrant Intestinal stem cell (ISC) proliferation and the expansion of the crypt domain. Using this system, we found that Tacc3 is required for the proper mitosis of Apc-deficient ISCs, and its disruption significantly attenuated the expansion of the crypt domain. In vivo analysis of corresponding mutant mice demonstrated that Tacc3 disruption led to a significant decrease in tumor number and prolonged survival. These observations demonstrated that Tacc3 is a potential chemotherapeutic target for intestinal tumors by perturbing the aberrant cell proliferation of Apc-deficient ISCs.
|
Report
(4 results)
Research Products
(16 results)
-
[Journal Article] Suppression of intestinal tumors by targeting the mitotic spindle of intestinal stem cells.2016
Author(s)
1.Yao, R., Oyanagi, J. Natsume, Y. Kusama, D., Kato, Y., Nagayama, S. & Noda, T.
-
Journal Title
Oncogene
Volume: Epub ahead of print
Issue: 47
Pages: 1-11
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
-
-
[Journal Article] Novel retinoblastoma mutation abrogating the interaction to E2F2/3, but not E2F1, led to selective suppression of thyroid tumors.2014
Author(s)
Toki H, Inoue M, Minowa O, Motegi H, Saiki Y, Wakana S, Masuya H, Gondo Y, Shiroishi T, Yao R, Noda T
-
Journal Title
Cancer Science
Volume: 105
Issue: 10
Pages: 1360-1368
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] A small compound targeting TACC3 revealed its different spatiotemporal contributions for spindle assembly in cancer cells.2014
Author(s)
Yao R, Kondoh Y, Natsume Y, Yamanaka H, Inoue M, Toki H, Takagi R, Shimizu T, Yamori T, Osada H, Noda T
-
Journal Title
Oncogene
Volume: in press
Issue: 33
Pages: 1-11
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-