The metabolic function of RB in controlling mevalonate (MVA) pathway regulates tumor progression

2014 Fiscal Year Final Research Report

• Project/Area Number: 25830076
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Kanazawa University
• Principal Investigator: SASAKI Nobuari 金沢大学, がん進展制御研究所, 博士研究員 (40415170)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: コレステロール / メバロン酸経路 / 悪性進展 / 細胞内ROS / RB / 前立腺がん / 癌幹細胞 / コレステロールエステル

Outline of Final Research Achievements

Recent advances in cancer metabolism have revealed that metabolic abnormalities in cancer cells are closely related to enhanced cell proliferation and malignant progression of a number of tumors.
Mutations in Retinoblastoma (RB) gene are found at the initiation of limited human cancers, whereas RB protein inactivation is frequently found in much wider variety of cancers mainly during their progression. These findings suggest that RB exerts more roles than previously thought. Here we show that RB affects transcription of many enzymes involved in Mevalonate (MVA) pathway. We demonstrate that RB depletion in prostate cancer cells induces some of typical malignant features including tumor sphere forming-activity and hormone-refractory growth. Cholesterol and its derivatives generated by MVA pathway contribute to these phenotypes through modifying cellular ROS level.
These results indicate that RB regulates cancer progression through the metabolic function in controlling MVA pathway.

Free Research Field

腫瘍生物学