Elucidation of renal tumorigenesis under FLCN deficiency

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09694
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Yokohama City University
• Principal Investigator: HASUMI Hisashi 横浜市立大学, 医学部, 助教 (40749876)
• Co-Investigator(Kenkyū-buntansha): 矢尾 正祐 横浜市立大学, 医学研究科, 客員教授 (00260787)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 遺伝性腎癌 / BHD症候群 / シングルセル発現解析 / がん微小環境 / 免疫チェックポイント阻害剤 / 腫瘍内不均一性

Outline of Final Research Achievements

We have identified novel FLNC ineracting partners and are investigating physiological meaning of those interactions using animal models. Furthermore, we have conducted single cell RNA-seq of BHD-associated kidney cancer and found that BHD-associated kidney cancer exhibits molecular proflinig simlimar to that of intercalating cell of collecting duct, transcriptomic intratumor heterogeneity (tITH) and differentially expressed genes including SLC4A4, HERC1, PLAAT4 and MIF. We also revealed distinct tumor microenvironment which is unique to each hereditary kidney cancer. These findings provides mechanistic insights into renal tumorigenesis as well as an oppotunity to develop novel therapeutics and diagnostics to hereditary nad sporadic kidney cancers.

Free Research Field

腎癌

Academic Significance and Societal Importance of the Research Achievements

本研究により、FLCNの膜輸送における役割が解明され、今後、膜輸送という全く新しい経路を標的とした新規腎癌治療薬の開発が期待できます。さらに今回のシングルセル発現解析により、詳細な腎腫瘍化機構の解明がなされただけでなく、免疫環境を含めたがん微小環境が明らかとなりました。これらの発見は腎癌細胞に対する新規治療薬開発ならびに免疫チェックポイント阻害剤や血管新生阻害剤などの腎癌の標準薬物療法の精密化につながります。