The roles of ELOVL2 in the progression of renal cell carcinoma

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16774
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: University of Tsukuba
• Principal Investigator: Kandori Shuya 筑波大学, 医学医療系, 講師 (50707825)
• Research Collaborator: Shimano Hitoshi ; Matsuzaka Takashi
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 腎癌 / 脂質代謝 / 脂肪酸伸長酵素 / ELOVL2

Outline of Final Research Achievements

Elongation of very-long-chain fatty acids (ELOVLs) catalyzes the elongation of very long-chain fatty acids and is required for various functions of normal organs by changing fatty acid composition of lipids. A hallmark of clear cell renal cell carcinoma (ccRCC) is the presence of intracellular lipid droplets. However, the roles of ELOVLs remain unexplored in ccRCC. We analyzed the expression of ELOVL 1-7 in tissues of tumor and non-tumor. ELOVL2 was especially highly expressed in the tissues of ccRCC. ELOVL2 knockout suppressed cell proliferation in renal cancer cells in vitro and tumor growth in mouse xenograft model. We demonstrated that ELOVL2 promoted cell proliferation through the suppression of apoptosis. Moreover, the high expression of ELOVL2 was significantly associated with a poorer prognosis in patients with ccRCC. These results give new insights on mechanism of tumor progression through lipid metabolism.

Free Research Field

泌尿器科学

Academic Significance and Societal Importance of the Research Achievements

癌と脂質代謝との関連については、新規の脂肪酸合成（脂質の「量」）が癌では亢進していることは数多く報告されている一方で、脂質の「質」と癌との関係は未だ十分に解明されていない。特に、本研究で着目したELOVLsに関する研究は腎癌のみならず他癌種でも未だ報告が非常に少なく、学術的独創性が高いと考えられる。また、脂肪酸はエネルギー源のみならず、生体膜成分やシグナル分子として多彩な生理機能を有しており、本研究を通して腎癌の悪性化における脂質代謝の分子機構が明らかになると期待される。また、ELOVL2による脂質の「質」の変化と腎癌の悪性化との関連が明らかになれば、新規治療開発の一助になる可能性が高い。