Potential roles of beta-arrestin pathway in colorectal cancer

• Project/Area Number: 18K08546
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Sakamoto Wataru 福島県立医科大学, 医学部, 講師 (40622337)
• Co-Investigator(Kenkyū-buntansha): 岡山 洋和 福島県立医科大学, 医学部, 講師 (20583397)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 大腸癌 / β-arrestin / arrestin-biased receptor / colon cancer cell / breast cancer cell / βアレスチン / 乳癌

Outline of Final Research Achievements

β-arrestins were first thought to only regulate desensitization and internalization of G protein coupled receptors (GPCR). It has recently been demonstrated that β-arrestins can activate PI3K, AKT and ERK signaling, independent of GPCR. In the present study, although cell models of β-arrestin 1/2-specific activation remain to be established in our laboratory, we addressed the clinical and genomic roles of β-arrestin 1/2 in colorectal cancer. We found that KRAS-mutant tumors as well as CMS3 tumors demonstrated significantly decreased levels of β-arrestin 2 expression in multiple cohorts of colorectal cancer.

Academic Significance and Societal Importance of the Research Achievements

癌細胞において重要なシグナル伝達を媒介すると思われるβアレスチンについて、その意義を解明することは、癌の生物学的機構の理解を深めることだけでなく、将来の癌治療にも寄与し得ると考える。特に大腸癌におけるドライバー変異や分子サブタイプとの関連が大腸癌治療の個別化への端緒となることを期待する。

Research Products

• [Presentation] Chromosomal instability causes deletion of tumor suppressor genes in colorectal cancer (2020)
  • Author(s): 岡山洋和, 遠藤英成, 加瀬晃志, 山内直人, 松本拓朗, 早瀬傑, 藤田正太郎, 遠藤久仁, 坂本渉, 齋藤元伸, 佐瀬善一郎, 門馬智之, 三村耕作, 大木進司, 河野浩二.
  • Organizer: 第120回日本外科学会定期学術集会
• [Presentation] dMMR 大腸癌再発例における癌微小環境の特徴 (2020)
  • Author(s): 遠藤英成, 岡山洋和, 加瀬晃志, 山内直人, 山田玲央, 氏家大輔, 坂本渉, 藤田正太郎, 遠藤久仁, 齋藤元伸, 佐瀬善一郎, 門馬智之, 三村耕作, 大木進司, 河野浩二.
  • Organizer: 第120回日本外科学会定期学術集会