Elucidation of the molecular mechanism of anaplastic transformation by comprehensive gene expression analysis and development of novel therapeutic strategies for anaplastic thyroid cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10541
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Shinshu University
• Principal Investigator: Ito Ken-ichi 信州大学, 学術研究院医学系, 教授 (10334905)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 甲状腺癌 / 未分化癌 / 未分化転化 / 新規治療戦略 / 網羅的遺伝子発現解析 / 稀少癌 / 分子腫瘍学 / 浸潤

Outline of Final Research Achievements

To develop a novel therapeutic strategy for anaplastic thyroid cancer, we analyzed molecular mechanism of anaplastic transformation of thyroid cancer. We identified a transcriptional regulatory factor, PATZ1, by comprehensive gene expression analysis of clinical specimens. Suppression of PATZ1 in normal thyroid follicular epithelial cell line and differentiated cancer cell line increased cell proliferation, migration, and invasion. In contrast, the introduction of PATZ1 gene in anaplastic thyroid cancer cell lines decreased cell proliferation, migration, and invasion of the cells. Besides, the regulation of uPA and MMPs activity by PATZ1 was demonstrated in vitro. On the other hand, the analysis of clinical specimens also showed a decrease in PATZ1 expression in parallel with the progression of the dedifferentiation of thyroid tumors. These results indicated that PATZ1 might be suppressively involved in carcinogenesis and the dedifferentiation of thyroid follicular epithelial cells.

Free Research Field

外科腫瘍学（甲状腺癌・乳癌）

Academic Significance and Societal Importance of the Research Achievements

甲状腺癌未分化癌は極めて悪性度が高いにも関わらず、orphan diseaseでもあり治療戦略の開発が進んでいない。今回の研究結果から、転写調節因子PATZ1の発現低下が甲状腺濾胞上皮細胞の癌化や甲状腺癌の脱分化を促進していることが示された。濾胞上皮細胞や分化癌細胞でPATZ1の発現が低下する機序は不明であるが、PATZ1の発現を維持、または回復させることで、甲状腺癌の進展の抑制や「未分化転化」の制御が得られる可能性が示唆され、未分化癌に対する新たな治療戦略創出の端緒となる知見が得られた。今後、PATZ1の制御機構が解明できれば、甲状腺癌患者の予後改善に向けた臨床応用が期待できる。