Fluctuation of ectodomain shedding and the emersion of cancer cell heterogeneity

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15221
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Ehime University
• Principal Investigator: Higashiyama Shigeki 愛媛大学, プロテオサイエンスセンター, 教授 (60202272)
• Co-Investigator(Renkei-kenkyūsha): NAKAYAMA HIROINAO 愛媛大学, プロテオサイエンスセンター, 助教 (40512132)
• Research Collaborator: FUKUDA SHINJI 愛媛大学, プロテオサイエンスセンター, 講師 (70398238)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: がん細胞の不均一性 / 乳がん細胞 / ゆらぎ / EGFファミリー / エクトドメイン・シェディング / amphiregulin / CUL3 / RhoA

Outline of Final Research Achievements

Cancer is derived a single cell and becomes to show heterogeneous population during the growth of its mass in general, which seems to lead to drug resistance. The epidermal growth factor (EGF) family are transmembrane growth factors and their ectodomain shedding is a crucial event to determine their soluble growth factor levels. We speculate that the fluctuation of the ectodomain shedding of the EGF family would be related to the emersion of heterogeneous population of cancer. In this study, we at first established three clones, stem, basal and luminal types, form human breast cancer cell line, MCF-7 cells, and then performed quantitative analysis of the ectodomain shedding of EGF family ligands in these clones. We revealed that the ectodomain shedding of proAREG uniquely showed the correlation between the shedding level and clone types, and was regulated through actin dynamics by CUL3 -RING based E3 ubiquitin ligase-dependent Rho activation.

Free Research Field

生化学、分子腫瘍学