Novel cancer therapy to target ROS from unhealthy mitochondria

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10542
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Gifu University
• Principal Investigator: FUTAMURA MANABU 岐阜大学, 大学院医学系研究科, 准教授 (10415515)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: Mieap / ｐ５３ / Breast Cancer / promoter methylation

Outline of Final Research Achievements

Mieaphas been known for involvement of mitochondrial quality control (MQC). We investigated the potential role of Mieap, a downstream of p53, in breast cancer. First, we observed the phenotype of breast cancer cell lines after infected with Ad-Mieap in vitro. Overexpression of Mieap induced caspase-dependent apoptosis in a moi-dependent manner. Particularly, NIX, a co-factor of MQC, is associated with Mieap-induced apoptosis. Second, Mieap expression was decreased in invasive ductal carcinoma less than ductal carcinoma in situ and fibroadenoma by immunohistochemistry. Breast cancer patients with impaired p53/Mieap-regulated MQC showed shorter disease-free survival than those without the MQC pathway. These findings demonstrated that Mieap may play an important role in MQC in cancer

Free Research Field

分子腫瘍学乳腺外科

Academic Significance and Societal Importance of the Research Achievements

がん細胞のミトコンドリア機能不全はWarburg 効果の一端を表しており、がんの特徴である。今回Mieapは多量発現で癌細胞にアポトーシスを誘導した。一方少量ではミトコンドリアの修復に携わっており、Mieapの重要な腫瘍抑制作用と考える。癌種による違いも明らかになってきた。これらは癌種による違いも明らかになってきており臨床応用のための重要な基礎データになっていくと考える。