Molecular mechanisms of adaptation to nutrient stress in ER-positive breast cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23896
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Keio University
• Principal Investigator: SAITO Yasuhiro 慶應義塾大学, 政策・メディア研究科(藤沢), 特任講師 (30613004)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 乳がん / アミノ酸トランスポーター / 細胞極性タンパク質

Outline of Final Research Achievements

LLGL2-SLC7A5 pathway plays a critical role for ER+ breast cancer cells to proliferate under nutrient stress condition. Since the association between LLGL2-SLC7A5 is enhanced by nutrient stress, this study aims to understand how LLGL2-SLC7A5 interaction is enhanced by nutrient stress. LLGL2 is phosphorylated at several amino acid residues, and the phosphorylation of LLGL2 affects the intracellular localization of LLGL2. Therefore, based on the hypothesis that phosphorylation of LLGL2 could change the affinity to SLC7A5, we examined the phosphorylation status of LLGL2 with stimulation by nutrient stress. However, we could not detect a drastic change in the phosphorylation level of LLGL2 in ER+ breast cancer cells. Next, we explored LLGL2-binding proteins that are activated by nutrient stress. We identified a candidate molecule that responds to nutrient stress.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

LLGL2-SLC7A5経路における、LLGL2の活性化分子機構の一端を明らかにすることはER陽性乳がん細胞、そして、抗がん剤が効かなくなった乳がん細胞に対する新しい治療法・治療薬の開発に大きく貢献すると考えられる。よって、本研究により得られた知見はLLGL2-SLC7A5経路を標的としたER陽性乳がん細胞の新規治療法・新規治療薬の開発に役立つと考えられることから、社会に貢献できる知見であることが示唆される。