Correlation between Notch signaling and chemo-resistance in Esophageal cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18086
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Osaka University
• Principal Investigator: Norihiro Matsuura 大阪大学, 医学部附属病院, 医員 (90804477)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: Notchシグナル / 上皮間葉転換 / 抗癌剤耐性

Outline of Final Research Achievements

In human esophageal cancer cell lines and mouse esophageal cancer subcutaneous tumor models, Notch3 expression and activity were both decreased by the anticancer drug 5-FU. The same result was observed in the 5-FU resistant cell line. Their expressions of EMT markers were up-regulated. In clinical samples after chemotherapy, Notch3 activity decreased and correlated with poor response to anticancer drugs, as did expression of EMT markers, and the same was true when Notch1 activity was increased in combination with decreased Notch3 activity. When Notch3 activity was increased, the effect of 5-FU was enhanced and the induction of EMT was inhibited in the cell line and mouse model. I also found that Notch3 directly regulates Vimentin.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

集学的治療の進歩に伴い食道癌治療の成績は向上しつつあるが、十分ではない。その一つの要因として抗癌剤による治療抵抗性が挙げられる。今回、抗癌剤耐性と関連のあると言われているEMTを制御するNotchシグナルに着目し、メカニズムを追求し治療へと活かすことのできる可能性を見出した。この結果は、食道癌の予後改善につながる糸口になりうるかもしれない。