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Research progress

2012-2013: Proposed research project 17

Functional analysis of the tumor suppressor APC in epithelial tubulogenesis and colorectal tumorigenesis
Leader : Yoshihiro Kawasaki
Research progress

In this research project, we have so far obtained the following findings. First, we have found that Asef is overexpressed in colorectal tumors and Notch3 up-regulates Asef expression by activating the Asef promoter in colorectal tumor cells. Second, we have shown that microRNA-1 (miR-1) is down-regulated in colorectal tumors and that miR-1 has the potential to suppress Notch3 expression through direct binding to its 3’-UTR region. Finally, we have shown that the miR-1-Notch3-Asef pathway is important for colorectal tumor cell migration (PLoS One, 2013). These results suggest that Asef may be a promising molecular target for the treatment of colorectal tumors. Furthermore, we have found that endothelial Notch ligand (DLL4) has the potential to induce colorectal tumor cell migration via Notch3 and Asef. The interaction between cancer cells and their microenvironment has a critical role in tumor development and progression. It is therefore tempting to speculate that Notch3-Asef signaling may be connected with the invasive behavior of colorectal cancer cells.