Elucidation of structure-function relationship of multidrug resistance-associated protein HSPB1 and its clinical application

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K01955
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomolecular chemistry
• Research Institution: Osaka Medical and Pharmaceutical University
• Principal Investigator: SAKAI Akiko 大阪医科薬科大学, 医学部, 講師 (30225750)
• Co-Investigator(Kenkyū-buntansha): 田中 覚 大阪医科薬科大学, 医学部, 非常勤講師 (50595741)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: HSPB1 / 抗癌剤耐性

Outline of Final Research Achievements

We investigated the function of the heat shock protein HSPB1 in the acquisition of resistance to the anticancer drugs 5-fluorouracil and paclitaxel, which have different mechanisms of action. Specifically, we analyzed the phosphorylation and oligomeric structure of HSPB1, as well as the proteins that interact with HSPB1. The results showed that the oligomeric structure and phosphorylation status of HSPB1 were different between sensitive and resistant cells, and that the oligomeric structure and interactions with interacting proteins also differed depending on the anticancer drug.

Free Research Field

生物学

Academic Significance and Societal Importance of the Research Achievements

多くの癌の治療法として抗癌剤による化学療法が重要であるが、抗癌剤に対する感受性の低下（耐性獲得）が治療上の問題となる。5-FUは大腸癌・乳癌など多くの癌で用いられる抗癌剤であるが、長期・反復投薬によって耐性を獲得する。その機序として5-FUが阻害する核酸代謝酵素の発現亢進が報告されているが、それが観察されない耐性も存在する。本研究の研究成果は耐性獲得機序の解明に貢献すると考えられる。