Development of intestinal tumor therapy targeting TACC3

2015 Fiscal Year Final Research Report

• 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
• Keywords: 消化管腫瘍 / 分子標的治療

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.

Free Research Field

細胞生物学