Suppression of colon cancer stemness by caudal-related homeobox transcription factors CDX1 and CDX2

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06955
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: University of Fukui
• Principal Investigator: Kazuya Hori 福井大学, 学術研究院医学系部門, 助教 (50749059)
• Co-Investigator(Kenkyū-buntansha): 青木 耕史 福井大学, 学術研究院医学系部門, 教授 (40402862)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 大腸癌 / CDX1 / CDX2

Outline of Final Research Achievements

Caudal-related homeobox transcription factors CDX1 and CDX2 are expressed specifically in the intestinal epithelial cells and essential for their development and homeostasis. In this study, we have investigated the mechanisms by which CDX1 and CDX2 suppressed malignant progression of colorectal tumorigenesis, and found that they suppressed cancer stemness of colon cancer cells. We have also found that CDX1 and CDX2 suppressed expression of cancer stemness-related genes directly but not through typical epigenetic mechanisms such as histone modification, suggesting a new mechanism that controls colon cancer stemness.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、腸管の上皮細胞の恒常性の維持に重要な役割を担うCDX1やCDX2が、大腸癌の悪性化や腫瘍幹細胞性を抑制することを見出した。また、その機構として、CDX1やCDX2が、典型的なエピジェネティックな遺伝子発現制御とは異なる機構により、大腸癌の腫瘍幹細胞性に関わる遺伝子の発現を制御していることを見出した。すなわち、従来の研究からは分からなかった、新たな大腸癌の悪性化や腫瘍幹細胞性の制御機構が解明できる可能性があり、新たな治療標的の同定などが期待できる。