Changes of tight junctions induced by extracellular stimuli determine cell shape and fate.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08693
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Sapporo Medical University
• Principal Investigator: SAWADA NORIMASA 札幌医科大学, 医学部, 教授 (30154149)
• Co-Investigator(Kenkyū-buntansha): 村田 雅樹 札幌医科大学, 医学部, 講師 (10404592)
• Research Collaborator: TAKASAWA KUMI ; AKIMOTO TAISHI
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: タイト結合 / JAM-A / claudin / occludin / tricellulin

Outline of Final Research Achievements

The tight junction (TJ) is an intercellular junction that works as a barrier to external stimulation and as a fence to maintain cell polarity. Recently, aberrant expression of TJ proteins have been reported in various diseases. In this study, we focused mainly on aberrant expression in human tumor and clarified the following. TJ proteins could be diagnostic markers for some tumors including hepatocellular carcinoma, intrahepatic cholangiocarcinoma, lung adenocarcinoma, cervical adenocarcinoma and salivary gland tumors. These findings suggested that TJ proteins are promising targets of cancer therapy. Furthermore, the expression of TJ proteins were involved in the enhancement of the malignancy of carcinoma such as invasion and proliferation. These findings suggested that abnormality of TJ might be involved in tumorigenesis.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

ヒト癌における細胞間接着装置タイト結合の構成分子の役割を検討し、膵癌ではtricellulin、肺癌ではJAM-A、胆管癌ではclaudin-18が、癌の進行に関与していること、子宮頚部腺癌ではclaudin-1が予後不良因子でGRP30を介してエストロゲン依存性に発現していることを明らかにした。これらは、各タイト結合分子が診断マーカー又は治療標的分子となりうることを意味し、急増する種々の癌に対する新しい治療戦略を提案するもので、社会的影響や意義は大きい。