Identification and functional analysis of nuclear pore complex components that function to transport beta-catenin between cytoplasm and nucleus

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15493
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kanazawa University
• Principal Investigator: Minamoto Toshinari 金沢大学, がん進展制御研究所, 教授 (50239323)
• Co-Investigator(Renkei-kenkyūsha): WONG Richard 金沢大学, 自然システム系, 教授 (30464035) ; ISHIGAKI Yasuhito 金沢医科大学, 総合医学研究所, 教授 (20232275) ; OHTA Tetsuo 金沢大学, 医学系, 教授 (40194170) ; MIYASHITA Tomoharu 金沢大学, 附属病院, 助教 (30397210)
• Research Collaborator: DOMOTO Takahiro 金沢大学, がん進展制御研究所, 助教 (80635540)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 大腸がん / β-カテニン / 核移送 / 核膜孔複合体

Outline of Final Research Achievements

To understand the mechanism by which β-catenin with no nuclear localization signal transits between cytoplasm and nucleus, this study investigated expression of and interaction between β-catenin and nucleoporins (Nups) that constitute nuclear pore complex and participate in nucleocytoplasmic trafficking of various functional macro-molecules. Comparative analysis of expression of 30 Nups in normal cells, colon cancer cell lines, human colorectal cancer (CRC) tissues and the non-neoplastic mucosa found an inverse association between the expression of a certain Nup (here called NupX) and the nuclear accumulation of β-catenin in colon cancer cells and CRC tissues. Subsequent analysis identified NupX among Nups coimmunoprecipitated with β-catenin and T-cell factor (Tcf)4 in protein extracts from colon cancer SW480 and HCT116 cells. Analysis of its expression and function indicated that NupX functions to excrete β-catenin from nucleus, thereby inactivating the Wnt signal pathway in CRC.

Free Research Field

腫瘍外科学