Mechanism of suppression of Notch signaling by CDX1 and CDX2 in colon cancer cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K18415
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: University of Fukui
• Principal Investigator: Hori Kazuya 福井大学, 学術研究院医学系部門, 助教 (50749059)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 大腸癌 / CDX1 / CDX2 / Notchシグナル

Outline of Final Research Achievements

In this study, we found that CDX1 and CDX2, which are homeobox transcription factors expressed in intestinal epithelial cells, directly regulate Notch signaling via RBP-J, an effector of Notch signaling. In addition, through mass spectrometry analysis of CDX2, we identified a NAD-dependent deacetylase Sirtuin1, which has been reported to regulate the Notch signaling in several cancers. We showed that, in HCT116 cells, CDX2 strongly suppresses the Notch activity, while Sirtuin1 inhibits the suppression of Notch by CDX2. These results suggest that CDX1 and CDX2 at least partially compete Sirtuin1 to regulate the activity of Notch signaling in colon cancer cells.

Free Research Field

腫瘍学