The relationship between the guidance molecules Draxin-Neogenin pathway and tumorigenicity of the small cell lung cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21287
• Project/Area Number (Other): 18H06182 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0901:Oncology and related fields
• Research Institution: Kumamoto University
• Principal Investigator: Sato Younosuke 熊本大学, 大学院生命科学研究部(医), 助教 (00823311)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: 小細胞肺癌 / 神経ガイダンス分子 / Draxin / Neogenin / 発癌

Outline of Final Research Achievements

To examine the relationship between Draxin-Neogenin signal pathway and the tumorigenicity of small lung cell carcinoma, we constructed deletion of Draxin gene SCLC cell lines and Neogenin gene SCLC cell lines. These cell lines are H69AR and SBC5, and we analyzed the protein expression amount and phosphorylation amount by western blotting and phosphor-kinase array kit. The deletion of Draxin gene was indicated that the expression of caspase, apoptosis-regulating factor, was decreased and the deletion of Neogenin gene reduced the expression of focal adhesion kinase which involves in tumor infiltration and metastases. Moreover, we constructed a decoy-protein which inhibits Draxin-Neogenin signal pathway and added decoy-protein to cultured SCLC cells. This examination exhibited a decrease in the expression of caspase.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

小細胞肺癌は高悪性度腫瘍であるが、従来の化学療法では治療効果が不十分であり、新規治療法の開発が求められている。ガイダンス分子は受容体との結合により細胞増殖やアポトーシスを調節することから、新しい癌治療のターゲットとして注目されているが、Draxin-Neogenin経路と小細胞肺癌に関する報告はこれまで存在しなかった。本研究によりDraxin-Neogenin経路は小細胞肺癌の腫瘍生存性においてアポトーシス調節や腫瘍の浸潤。転移能に関与している可能性があることがわかり、小細胞肺癌の新規治療法開発のターゲットとしての可能性も示すことができた。