Studies on metastasis of colorectal cancer stem cells using clinical materials and mouse models

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06948
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Kyoto University
• Principal Investigator: Fumihiko Kakizaki 京都大学, 医学研究科, 助教 (00609076)
• Co-Investigator(Kenkyū-buntansha): 武藤 誠 公益財団法人田附興風会, 医学研究所, 所長 (70281714)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: がん幹細胞 / TRIO / 予後不良 / 大腸がん / がん転移

Outline of Final Research Achievements

We conducted an analysis of metastasis mechanisms and an exploration of crosstalk mechanisms with TRIO signaling using cancer stem cell lines derived from TRIO(pY2681)-positive colorectal cancer patients with poor prognosis. These analyses provided representative gene expression profiles of cancer stem cells derived from these patients, as well as marker genes associated with patient survival. Additionally, four candidate metastasis markers that may suppress liver metastasis were identified. Since these metastasis markers were not protein-modifying enzymes, they were unlikely to directly affect TRIO signaling, making it challenging to discover metastasis inhibitors targeting them. Moving forward, we intend to advance the analysis of metastasis inhibitor candidates identified through an alternative strategy.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は学術的に十分には解明されていない大腸がん転移機序の一部を、患者由来がん幹細胞を用いて明らかにするだけでなく、治療方針を決めるバイオマーカーや転移阻害薬の候補を同定している点において臨床医学的に重要性が高い。このように転移機構を明らかにしていくことで、再発リスクの高いがん患者に対する個別化補助化学療法等への応用に繋がることが期待される。