Genetic analysis of tumor progression by inter-organ communication

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07120
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kyoto University
• Principal Investigator: Kiichiro Taniguchi 京都大学, 生命科学研究科, 特定講師 (20554174)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: がん遺伝子Ras / 化学受容器 / 臓器連関 / ショウジョウバエ

Outline of Final Research Achievements

We found that the haploid mutants of chemoreceptor genes, such as odorant receptor, gustatory receptor and ionotropic receptor drives the overgrowth of RasV12 clone in Drosophila. However, the mechanism which links the haploid mutation of chemoreceptor and the overgrowth of RasV12 clone has been unclear. Here, we demonstrated that the oncogenic overgrowth of RasV12 clones occurring in haploid mutants of chemoreceptor genes are responsible for the neuronal loss of chemoreceptor genes. The loss of chemoreceptors leaded to the defects in the resistance to the high-sugar diet, implying that the loss of chemoreceptors caused the defects in a systemic sugar metabolism. Importantly, the glycolysis pathway is required for the overgrowth of RasV12 clones generated in haploid mutants of chemoreceptor genes. We also found that the overgrowth of RasV12 clone was regulated through the suppression of the Hippo signaling pathway.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

発がんリスクの上昇・低下には全身性の多臓器連関が関与している可能性という事が、多くの統計データによって示唆されており、運動による発がんリスク低下や肥満による発がんリスク上昇などが代表例として挙げられる。一方で、多臓器連関によるがん制御の分子メカニズムについては未解明な点が多く、人為的介入によるがん予防・治療への課題は多い。本研究では、嗅覚・味覚のセンサーとして働く化学受容器の喪失が「ニューロン―がん原発巣」の臓器連関を介してRas腫瘍の悪性化を引き起こすという、新たながん原性の臓器連関メカニズムを明らかにした。本研究成果は、がんリスクの遺伝的指標やがん治療・予防の新規標的として期待される。