The role of NADPH oxidase 5 and intracellular transportation of ROS in tumor progression of colon cancer

• Project/Area Number: 20K17609
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Shimizu Hiroki 京都府立医科大学, 医学(系)研究科(研究院), 助教 (00756827)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 大腸癌 / NADPH Oxidase 5 / 細胞浸潤能 / mRNAマイクロアレイ / ILK signaling pathway / 細胞増殖能 / NADPH oxidase 5

Outline of Research at the Start

本研究は、活性酸素種の産生に関与するNADPH oxidase 5(NOX5)の大腸癌における発現・機能、ならびに産生された活性酸素種の細胞内輸送機構を解析し、大腸癌進展への関与を解明するという、世界的にもこれまでにない斬新な視点からの研究であると言える。もし、NOX5ならびに産生される活性酸素種が大腸癌の癌進展に関与していることが判明すれば、NOX5機能ならびに活性酸素種輸送機構の制御が新たな大腸癌治療としての標的となる可能性を秘めている。

Outline of Final Research Achievements

This study aimed to clarify the relationship between NOX5 and cancer development using an in vitro model. Real-time quantitative PCR was performed to determine the NOX5 expressions levels of colon cancer cell lines. NOX5 knockdown experiments were conducted, and the impact on cell proliferation, migration, and invasion were analyzed. In addition, mRNA microarray was conducted to assess changes in gene profile. NOX5 mRNA expression was high in HCT116 cells and moderate in SW48 cells. NOX5 knockdown significantly inhibited cell migration and invasion in both HCT116 and SW48 cells; however, NOX5 knockdown reduced cell proliferation in only HCT116 cells. mRNA microarrays showed a strong relationship between NOX5 expression levels and integrin-linked kinase signaling pathways. The NOX5 expression in colon cancer cells affects cancer progression, especially cell motility. NOX5 may be a novel therapeutic target for the future development of treatments for colon cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究はヒト大腸癌細胞株を使用し、近年注目されている活性酸素種産生に関与するNOX5の大腸癌における発現・機能の解析を行い、大腸癌進展への関与を解明した初めての報告である。また、我々はヒト大腸癌組織でもNOX5発現が高度であれば予後不良となることをこれまでに確認、報告している。
今後、さらに研究を進めることによりNOX5機能の制御が新たな大腸癌治療としての標的となる可能性を秘めており、学術的・社会的意義は大きいものと考えられる。

Research Products

• [Journal Article] NADPH oxidase 5 has a crucial role in cellular motility of colon cancer cells. (2021)
  • Author(s): Ashizawa N, Shimizu H, Shoda K, Furuya S, Akaike H, Hosomura N, Kawaguchi Y, Amemiya H, Kawaida H, Sudo M, Inoue S, Kono H, Katsurahara K, Shiozaki A, Ichikawa D
  • Journal Title: International Journal of Oncology Volume: 59 Issue: 2 Pages: 63-63
  • DOI: 10.3892/ijo.2021.5243
  • Peer Reviewed
• [Presentation] The Significant Oncologic Role of NOX5 in Colon Cancer (2020)
  • Author(s): 清水浩紀
  • Organizer: 第79回日本癌学会総会