Study on the role of inflammation in gastrointestinal cancer and regeneration

2022 Fiscal Year Final Research Report

• Project/Area Number: 15K21775
• Research Category: Fund for the Promotion of Joint International Research (Home-Returning Researcher Development Research)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Hokkaido University (2017, 2021-2022); Keio University (2015, 2018-2020)
• Principal Investigator: Taniguchi Koji 北海道大学, 医学研究院, 教授 (20627020)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: 炎症 / がん / 組織再生

Outline of Final Research Achievements

We found that the Src family-kinase (SFK)-YAP pathway is activated by deletion of the tumor suppressor gene adenomatous polyposis coli (APC) in colorectal cancer. Using a tissue microarray (TMA) of human colon cancer samples, we found co-activation of SFK, YAP, STAT3, and Notch signals in about 70% of the samples. We also confirmed the increased expression of gp130 in human colorectal cancer samples compared to normal colon samples. In addition, we revealed that co-administration of SFK inhibitor and JAK inhibitor is more effective than single-agent inhibition in the treatment of colorectal cancer. These data suggest the importance of the gp130-SFK-YAP pathway in colorectal cancer.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

組織再生を促進するシグナルの多くは癌においても活性化している事が知られており、このシグナルが癌においても活性化していれば、癌の新しい治療標的になる可能性がある。今回の研究で、大腸がんにおいてもSrc family-kinase (SFK)-YAP経路が腫瘍抑制遺伝子 Adenomatous polyposis coli (APC)の欠損により誘導されることを明らかにしたので、このSFK-YAP経路が大腸がんにおけるがんの新規治療標的となる可能性がある。