Elucidation of the acquisition mechanism of undifferentiated traits in well-differentiated thyroid cancer and search for new biomarkers

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09632
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Kobe University
• Principal Investigator: Inase AKi 神戸大学, 医学研究科, 医学研究員 (90596181)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 甲状腺癌 / 未分化癌 / 脱分化 / 上皮間葉転換

Outline of Final Research Achievements

The purpose of this study was to elucidate the mechanism by which well-differentiated thyroid cancer acquires undifferentiated traits. First, by comparing gene expression between well-differentiated and undifferentiated sites using patient specimens that had undergone anaplastic transformation from well-differentiated cancer, I found that epithelial-to-mesenchymal transition (EMT) is involved in undifferentiated transformation; I focused on FOXD1 as a candidate factor related to the acquisition of undifferentiation traits. Experiments using thyroid cancer cell lines revealed the involvement of FOXD1 in EMT and the correlation with EMT transcription factors SNAI1/2. I also found that demethylation of the promoter region may be involved in regulating FOXD1 expression. Furthermore, I established a FOXD1 knockout cell line using CRISPR/Cas9 genome editing technology.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、甲状腺高分化癌が未分化形質を獲得する機序に関連する候補遺伝子としてFOXD1を見出した。FOXD1の発現調節により、EMTを制御できる可能性があることが示唆された。このことは治療法が確定しておらず、極めて予後不良である甲状腺未分化癌の新規治療法のターゲットとなる可能性がある。また、未分化癌の早期発見マーカーとして利用できる可能性もあり、今後の臨床応用が期待される。