Dysregulation of AKT network and its application for precision medicine in lung cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 17K08727
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: International University of Health and Welfare (2020-2021); Jichi Medical University (2017-2019)
• Principal Investigator: Dobashi Yoh 国際医療福祉大学, 国際医療福祉大学病院, 教授 (90231456)
• Co-Investigator(Kenkyū-buntansha): 北川 雅敏 浜松医科大学, 医学部, 教授 (50294971) ; 坪地 宏嘉 自治医科大学, 医学部, 教授 (50406055) ; 後藤 明輝 秋田大学, 医学系研究科, 教授 (90317090)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Keywords: Trefoil factor-1 / mTOR / 肺癌 / 増殖抑制 / 遊走 / 浸潤 / バイオマーカー

Outline of Final Research Achievements

We identified Trefoil factor 1 (TFF1) as a molecule negatively regulated by mammalian Target of Rapamycin (mTOR). In cultured cells, TFF1 was found to be negatively regulated by mTOR at promoter level by Luciferase assay. TFF1 functions as a suppressor of cancer proliferation, cell migration and invasion and thus, may provide a synergistic target for potential treatment strategies for human lung carcinoma. Although TFF1 was secreted only in adenocarcinoma cells in culture, its expression was observed in all histological types of human lung carcinoma tissues. Moreover, serum levels of TFF1,2,3 measured by ELISA were significantly higher in lung cancer patients than controls. Therefore, serum TFF1,2,3 levels are promising and predictive biomarkers, and their measurement provide a useful in vivo and non-invasive diagnostic screening.

Free Research Field

腫瘍病理学

Academic Significance and Societal Importance of the Research Achievements

TFF-1は肺癌培養細胞においてアポト－シスを誘導することで細胞増殖を抑制し、遊走、浸潤能も抑制した。TFF-1が肺癌細胞では腫瘍抑制性に機能するという新規の結果は、基礎研究面での意義だけでなく、TFF-1の発現、機能を亢進させる薬剤が肺癌における新たな抗癌剤の候補となり得るということで臨床応用が期待できる点でも意義がある。またTFF-1-3の血中濃度は肺癌のスクリーニング、あるいは治療後の再発や転移のモニターリングの際のバイオマーカーとなる可能性も示唆され、こちらは肺癌の診断、治療に大きく貢献できる可能性がある事で社会的にも非常に意義のある結果と考えている。