The effects of GBP-1 on dynamics of cancer cells in human salivary gland duct epithelium.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18777
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Ryo MIYATA 札幌医科大学, 医学部, 助教 (00610875)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 唾液腺癌 / 正常唾液腺管上皮細胞 / GBP-1 / 3細胞間タイト結合分子 / angulin-1/LSR / p63シグナル / 悪性化 / HDAC阻害剤

Outline of Final Research Achievements

Salivary gland cancer is relatively rare among all head and neck cancers, and new treatments are desired for unresectable cases and distant metastases.
Guanylate-binding protein-1 (GBP-1) is an interferon-inducible large GTPase involved in the epithelial barrier at tight junctions. To investigate the role of GBP-1 in normal human salivary gland duct epithelial cells, the cells were treated with the proinflammatory cytokines including IFNγ. GBP-1 plays a crucial role in barrier function of normal human salivary gland duct epithelium and it may perform a preventive role in cancers.The p53 family p63 gene is essential for the proliferation and differentiation of various epithelial cells, and it is overexpressed in some salivary gland neoplasia. Inhibition of Histone deacetylases (HDACs) and signal transduction pathways inhibited cell proliferation and migration, induced tight junctions, and promoted differentiation in p63-positive salivary duct adenocarcinoma (SDC).

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、GBP-1の唾液腺癌の悪性化における役割を解明できただけでなく、唾液腺癌の新規悪性化の機序解明により治療法の開発にも有用であった。