Analysis of NOTCH1 Signal in Esophageal Cancer Invasion

• Project/Area Number: 19K18156
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Nagoya City University
• Principal Investigator: Okubo Tomotaka 名古屋市立大学, 医薬学総合研究院(医学), 助教 (70770238)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 食道癌 / NOTCH1

Outline of Research at the Start

本研究の目的はβ-cateninが核に蓄積しない食道癌においてNOTCH1シグナル活性化が浸潤へ誘導する因子を同定することである。この目的を達成するための実験の概要を以下に示す。①臨床検体と細胞株を用いたNOTCH1シグナル亢進と食道癌浸潤能の相関②食道癌におけるNOTCH1が関与する遺伝子の検討③β-cateninが蓄積しない食道癌、およびβ-cateninをノックアウトした大腸癌におけるNOTCH1経路に関与する候補因子の同定④同定した候補因子の浸潤/増殖能における機能解析(in vitro, in vivo)⑤NOTCH1経路の抑制による抗癌作用の有効性の評価

Outline of Final Research Achievements

Clinical specimens of esophageal cancer were used to investigate whether there is a prognostic difference in the expression of NOTCH1. no clear causal relationship between NICD expression and prognosis was found. Esophageal cancer cell lines were used for forced expression or suppression of NOTCH1. WST-1 assay, Ki67, etc. were examined for proliferative potential, and Invasion assay and E-cadherin, etc. were examined for invasive potential, but no significant results were obtained.

Academic Significance and Societal Importance of the Research Achievements

本研究では食道癌におけるNOTCH1の意義の解明にはつながらなかった。