演題抄録

一般口演

開催概要
開催回
第56回・2018年・横浜
 

肺癌の新たな分子標的としての直鎖状ユビキチン合成酵素の有用性

演題番号 : O1-4

[筆頭演者]
演者)中澤 世識:1 
[共同演者]
清水 公裕:1、伊部 崇史:1、尾林 海:1、河谷 菜津子:1、矢島 俊樹:1、茂木 晃:1、調 憲:1

1:群馬大学・総合外科

 

Purpose: Linear ubiquitin (M1-ub) is a recently characterized type of posttranslational modification, which mainly regulates inflammatory signals through activation of NFκB signaling. M1-ub is specifically assembled by an enzyme complex known as linear ubiquitin chain assembly complex (LUBAC), composed of the proteins HOIP, HOIL-1L, and Sharpin. The role of M1-ub and LUBAC in lung cancer is unclear. We aimed here to identify the value of LUBAC as a molecular target in lung cancer treatment.
Methods: We measured the expression of LUBAC components in lung cancer cell lines to identify those with high LUBAC expression. We inhibited LUBAC activity both by siRNA and by use of a specific inhibitor of LUBAC activity and analyzed effect on tumor proliferation, migration, and apoptosis. We also searched for germline polymorphism of HOIP in lung cancer patients that reportedly elevate LUBAC activity.
Results: LUBAC expression was higher in adenocarcinoma cell lines compared to squamous cell carcinoma (2.42 vs 1.03, respectively, p=0.011). Knockdown of LUBAC in cell lines with high LUBAC expression decreased activation of NFκB and ERK signaling, resulting in lower proliferation (46.1% decrease, P<0.001) and migration (51.5% decrease, P=0.005). LUBAC knockdown also resulted in increased apoptosis via activation of caspases. Treatment with a LUBAC inhibitor showed similar results, with decreased proliferation, decreased migration, and increased apoptosis. We finally identified patients with a rare germline polymorphism of HOIP (2 out of 517 patients, 0.36 % incidence).
Conclusion: We identified that LUBAC is a regulator of proliferation, migration, and apoptosis in certain lung cancer cell lines. Inhibition of LUBAC is a potential molecular target in lung cancer treatment.

キーワード

臓器別:肺・縦隔・胸膜

手法別:基礎腫瘍学

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