Role of Smurf2-YY1 axis in regulating colorectal cancer metastasis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17640
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Chiba University
• Principal Investigator: Sato Nami 千葉大学, 大学院医学研究院, 特任助教 (40867272)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: YY1 / 大腸癌 / 転移 / ITGAV / ITGB1

Outline of Final Research Achievements

The aim of this study was to investigate the possibility that the ubiquitin proteasome system (UPS) E3 ligase Smurf2 acts as a tumor suppressor in colorectal cancer by degrading the transcription factor YY1 through the UPS and suppressing the epithelial-mesenchymal transition (EMT).
Contrary to the hypothesis, the relationship between Smurf2, YY1, and EMT was considered to be low in the examination using clinical specimens and cell lines. However, further analysis of YY1 function revealed that it has a tumor-suppressive role by suppressing colon cancer cell migration and invasion. Furthermore, microarray analysis confirmed that YY1 down-regulated ITGAV and ITGB1 genes, which are integrin family members related to cell adhesion and cancer metastasis.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

残念ながらUPS系やEMTに焦点をあてた大腸癌の転移メカニズム解明という目的は果たせなかった。一方で、大腸癌においてYY1がITGAVとITGB1の遺伝子発現を調節することで腫瘍抑制的役割を果たすことを示唆するデータはこれまで報告されておらず、新たな知見である。今後さらなる検証を重ねることで大腸癌の新たな転移機構を解明する一助になることが期待される。