Application of the CUL3-dependent cell growth system to breast cancer therapy

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18030
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Ehime University
• Principal Investigator: Nishiyama Kanako 愛媛大学, 医学部附属病院, 助教 (50763348)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: HER2 / EGFR / CNKSR1 / PTPRH / phosphatase / protein array

Outline of Final Research Achievements

CUL3 is a scaffold protein of the Cullin-RING type ubiquitin (Ub) ligase complex, which forms a complex with KCTD10 and leads to ubiquitination and proteolysis of RhoB. In this study, the detailed mechanism of cell proliferation was elucidated at the molecular level. Using human protein arrays prepared by wheat cell-free protein synthesis system, we succeeded in identifying CNKSR1, a scaffold protein regulated by RhoB, and PTPRH, an EGFR phosphatase. We identified the potential of novel molecular targeted drugs in HER2-positive breast cancer.

Free Research Field

乳腺外科

Academic Significance and Societal Importance of the Research Achievements

乳癌のうち約20%はHER2陽性乳癌であり、HER2陽性乳癌は一般的に増殖能が高く予後不良である。抗HER2薬の開発によりその予後は改善しているが、長期使用に伴う薬剤の耐性化などは未だ問題となっている。我々の研究において、HER2陽性乳癌における新規な増殖メカニズムを分子レベルで解明した。これらの分子を標的とした薬剤は、HER2陽性乳癌におけるHER2以外を標的とした新しい治療戦略となり得る。