Molecular basis of cancer malignancy via the activation of the hedgehog signaling pathway by the nucleoporin Nup88

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07700
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Sojo University
• Principal Investigator: Makise Masaki 崇城大学, 薬学部, 准教授 (80433001)
• Co-Investigator(Kenkyū-buntansha): 國安 明彦 崇城大学, 薬学部, 教授 (90241348)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Nup88 / Kif7 / ヘッジホッグ経路 / がん / Gli1

Outline of Final Research Achievements

We investigated the regulatory mechanism of Nup88 expression and its involvement in the progression of the cancer malignancy using prostate cancer cell lines and HeLa cells. In the former, the expression of Nup88 was unexpectedly suppressed by androgen, an exacerbation factor for prostate cancer, so we abandoned the analysis. For the latter, we found that overexpression of Nup88 suppressed Kif7 expression and promoted Gli1 expression, indicating that the hedgehog signaling pathway associated with cancer malignancy is activated. Since the knockdown of Kif7 promoted the Gli1 expression, it was suggested that overexpression of Nup88 may contribute to cancer malignancy by activating the hedgehog signaling through suppression of Kif7 expression.

Free Research Field

分子生物学、細胞生物学、生化学

Academic Significance and Societal Importance of the Research Achievements

Nup88の発現量とがんの悪性度には正の相関があると報告されている。しかしながら、Nup88ががんの悪性化にどのように寄与しているのかは不明であった。本研究は、Nup88がヘッジホッグ経路を活性化してがんを悪性化するという全く新しい可能性を示した点で重要である。この可能性に基づいた今後の研究展開によりNup88依存的なヘッジホッグ経路の活性化が明確になれば、ヘッジホッグ経路を標的にした新たな抗腫瘍薬の開発の基礎的知見となり得るだろう。