Functional analysis of ubiquitin E3 complex scaffold protein,Cullin-3 in breast cancer cells

• Project/Area Number: 17K16510
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Ehime University
• Principal Investigator: Murakami Akari 愛媛大学, 医学部附属病院, 助教 (60722593)
• Research Collaborator: Maekawa Masashi ; Kawai Katsuhisa ; Nakayama Jun ; Araki Nobukazu ; Semba Kentaro ; Taguchi Tomohiko ; Kamei Yoshiaki ; Takada Yasutsugu ; Higashiyama Shigeki
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 乳癌 / CUL3 / 細胞特性 / HER2陽性乳癌 / 乳癌細胞特性解析 / 乳癌細胞 / 細胞膜形態 / 幹細胞 / ユビキチンリガーゼ

Outline of Final Research Achievements

Human breast cancer can be classified by gene expression into four or five subtypes, and the treatment plans are decided based on the subtypes. From this standpoint, it is important to elucidate molecular mechanisms of the determination of breast cancer characteristics, which could lead to the development of novel therapy for breast cancers. In this research proposal, we focused on a ubiquitin E3 scaffold protein, cullin-3 (CUL3), and found that CUL3 is essential for Rac1 activation and cell proliferation specifically in HER2-positive breast cancer cells.

Academic Significance and Societal Importance of the Research Achievements

HER2陽性乳癌細胞で予後を規定するRac1の新しい活性化機構として、CUL3/KCTD10/RhoB軸の同定に成功した。今後は、CUL3/KCTD10依存的に活性化されるRac1の詳細な生理機能の解明が期待される。

Research Products

• [Journal Article] Cullin‐3/KCTD10 E3 complex is essential for Rac1 activation through RhoB degradation in human epidermal growth factor receptor 2‐positive breast cancer cells (2019)
  • Author(s): Murakami Akari、Maekawa Masashi、Kawai Katsuhisa、Nakayama Jun、Araki Nobukazu、Semba Kentaro、Taguchi Tomohiko、Kamei Yoshiaki、Takada Yasutsugu、Higashiyama Shigeki
  • Journal Title: Cancer Science Volume: 110 Issue: 2 Pages: 650-661
  • DOI: 10.1111/cas.13899
  • Peer Reviewed / Open Access
• [Presentation] CUL3型ユビキチンE3複合体はHER2陽性乳癌細胞におけるEGF刺激依存的な細胞膜形態変化を抑制する (2018)
  • Author(s): 村上朱里,、前川大志,、川合克久、荒木伸一、中山淳、 仙波憲太郎、田口友彦、亀井義明、高田泰次、東山繁樹
  • Organizer: 第５９回日本生化学 中国・四国支部例会
• [Presentation] Novel mechanisms of Rac1 activation by the cullin-3/KCTD10 ubiquitin E3 complex in HER2-positive breast cancer. (2018)
  • Author(s): Akari Murakami, Masashi Maekawa, Katsuhisa Kawai, Jun Nakayama, Nobukazu Araki, Kentaro Semba, Tomohiko Taguchi, Yoshiaki Kamei, Yasutsugu Takada, Shigeki Higashiyama
  • Organizer: San Antonio Breast Cancer Symposium