Analysis of novel post-translational modifications in colorectal cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07656
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Nagoya University (2021-2022); Aichi Cancer Center Research Institute (2019-2020)
• Principal Investigator: Mishiro-Sato Emi (佐藤恵美) 名古屋大学, トランスフォーマティブ生命分子研究所, 特任講師 (00455544)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 翻訳後修飾 / 大腸がん / プロテオミクス

Outline of Final Research Achievements

To explore new therapeutic targets for colorectal cancer, we aimed to elucidate the biological significance of variations in acylation modifications in colorectal cancer tumor tissues with the aim of developing novel colorectal cancer therapies.
To validate the clinical significance of the modification changes found in mouse models and to explore therapeutic targets, we performed proteomic analysis and comprehensive analysis of acylation-related post-translational modifications using colorectal tumor tissues from familial adenomatous polyposis (FAP) patients. Inhibition of NAT10, which was selected as a target, showed growth inhibition in tumor-derived organoids and colorectal cancer cell lines from FAP patients, and the mechanism is now being elucidated.

Free Research Field

Proteomics

Academic Significance and Societal Importance of the Research Achievements

大腸がんは、早期発見で治療をすれば治癒すると思われがちだが、死亡者数は年々増加し続けており、新しい治療法の標的探索が求められている。腫瘍部の遺伝子やタンパク質だけでなく、その翻訳後修飾に着目した本研究は新しい側面で大腸がんの治療標的を見出すことができたことから、メカニズム解明を進めることで新しい治療戦略の構築が期待される。