Emergence of anticancer drug resistance of ANXA1 for gastrointestinal tract cancers

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09099
• 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: ONOZAWA Hisashi 福島県立医科大学, 医学部, 助教 (50622338)
• Co-Investigator(Kenkyū-buntansha): 齋藤 元伸 福島県立医科大学, 医学部, 講師 (90611749)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 消化器癌 / ANXA1 / 抗癌剤耐性

Outline of Final Research Achievements

The family of Annexin is Ca2+/phospholipid-binding proteins that corporates with p53 on cancer development, progression, and metastasis. We found that elevated expression of Annexin A1, one of the annexin gene family, confers resistance to anticancer drugs. Because Annexin A1 expression is induced by ARID1A gene truncating mutations in breast cancer, we investigated the expression of both Annexin A1 and ARID1A to confirm their correlations in gastrointestinal cancer cells (gastric cancer). In addition, we performed immunohistochemical staining for Annexin A1 and ARID1a in surgically resected gastric cancer specimens. However, no correlation between Annexin A1 and ARID1A expressions was observed in cell experiment and gastric cancer tumor.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

アネキシンA１の高発現が抗癌剤耐性をもたらすことから、抗癌剤の治療を長く継続できるためにはアネキシンA1が発現誘導されないほうが良い。そのため、アネキシンA1の発現を誘導する上流の因子であるARID1Aとの関連の解明を試みた。その理由は、乳癌でARID1A遺伝子の失活型変異がアネキシンA1の発現を誘導するためである。胃癌細胞株でARID1Aをノックダウンすると、目的としたアネキシンA１は発現誘導されず、他のアネキシンA6などが発現誘導されていた。本研究ではアネキシンA1は抗癌剤の耐性に寄与するが、その経路を明らかにすることはできなかったので、さらなる検討が必要である。