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Targeting ubiquitin conjugating enzyme UbcH5b by a triterpenoid PC3-15 from Schisandra plants sensitizes triple-negative breast cancer cells to lapatinib.

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收录情况： ◇ SCIE

作者：
Huang Maobo[a,b] * ; Zhou Yuanfei[b,c] * ; Duan Dongzhu[d] * ; Yang Chuanyu[a] ; Zhou Zhongmei[a] ; Li Fubing[e] ; Kong Yanjie[f] ; Hsieh Yi-Ching[g] ; Zhang Ruihan[h] ; Ding Wenping[c] ; Xiao Weilie[h] ; Puno PemaTenzin[c] ; Chen Ceshi[a,i,*1] ;
机构： [a]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China [b]Kunming College of Life Sciences, University of Chinese Academy Sciences, Kunming, Yunnan, China [c]State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, China [d]Shaanxi Key Laboratory of Phytochemistry and College of Chemistry and Chemical Engineering, Baoji University of Arts and Sciences, Baoji, 721013, China [e]Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, 510095, China [f]Biobank, Shenzhen Second People’s Hospital/ the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, China [g]The Center for Cell Biology and Cancer Research, Albany Medical College, 47 New Scotland Ave, Albany, NY, 12208, USA [h]Key Laboratory of Medicinal Chemistry for Key Laboratory of Medicinal Chemistry for Natural Resource (Ministry of Education and Yunnan Province), State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Chemical Science and Technology, Yunnan University, 2 North Cuihu Road, Kunming, 650091, China [i]KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China
出处：
DOI： 10.1016/j.canlet.2021.02.009
ISSN：

关键词： HECTD3 UbcH5b Ubiquitination Autophagy Schisandraceae triterpenoid

摘要：
Increasing evidence suggested that a number of ubiquitin enzymes, including ubiquitin-activating enzymes, ubiquitin-conjugating enzymes, E3 ubiquitin ligases and deubiquitination enzymes contribute to therapeutic resistance in triple-negative breast cancer (TNBC) cells. Inhibition of these enzymes with small molecule inhibitors may restore therapeutic sensitivity. Here, we demonstrated ubiquitin conjugating enzyme UbcH5b strongly supports HECTD3 auto-ubiquitination in vitro. Based on this, we developed a Fluorescence Resonance Energy Transfer (FRET) assay and identified three Schisandraceae triterpenoids, including PC3-15, to block HECTD3/UbcH5b auto-ubiquitination. Furthermore, we revealed that PC3-15 directly binds to UbcH5b and also inhibits UbcH5b-mediated p62 ubiquitination. We found that the UbcH5b-p62 axis confers TNBC cells resistance to lapatinib by promoting autophagy. Consistently, PC3-15 inhibits lapatinib-induced autophagy and increases lapatinib sensitivity in TNBC in vitro and in mouse xenografts. These findings suggest that the UbcH5b-p62 axis provides potential therapeutic targets and that Schisandraceae triterpenoids may be used for TNBC treatment in combination with lapatinib. Copyright © 2021 Elsevier B.V. All rights reserved.

基金：
National Key Research and Development Program of China (2020YFA0112300 and 2018YFC2000400 to C. Chen), National Natural Science Foundation of China (82073316 to D. Duan; 81830087 and 31771516 to C. Chen; 81672639 to Z. Zhou; 81903541 to R. Zhang), project of Innovative Research Team of Yunnan Province (2019HC005) and Yunnan Applicative and Basic Research Program (2018FY001 to W. Xiao), China Postdoctoral Science Foundation (2019M662869 to F. Li).
语种：
外文
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中科院(CAS)分区：
出版当年[2021]版：
大类 | 1 区 医学
小类 | 2 区 肿瘤学
最新[2023]版：
大类 | 1 区 医学
小类 | 2 区 肿瘤学
JCR分区：
出版当年[2020]版：
Q1 ONCOLOGY
最新[2023]版：
Q1 ONCOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [a]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China [b]Kunming College of Life Sciences, University of Chinese Academy Sciences, Kunming, Yunnan, China
共同第一作者：
通讯作者：
通讯机构： [a]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China [i]KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China [*1]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
推荐引用方式(GB/T 7714)：
Huang Maobo,Zhou Yuanfei,Duan Dongzhu,et al.Targeting ubiquitin conjugating enzyme UbcH5b by a triterpenoid PC3-15 from Schisandra plants sensitizes triple-negative breast cancer cells to lapatinib.[J].CANCER LETTERS.2021,504:125-136.doi:10.1016/j.canlet.2021.02.009.
APA：
Huang Maobo,Zhou Yuanfei,Duan Dongzhu,Yang Chuanyu,Zhou Zhongmei...&Chen Ceshi.(2021).Targeting ubiquitin conjugating enzyme UbcH5b by a triterpenoid PC3-15 from Schisandra plants sensitizes triple-negative breast cancer cells to lapatinib..CANCER LETTERS,504,
MLA：
Huang Maobo,et al."Targeting ubiquitin conjugating enzyme UbcH5b by a triterpenoid PC3-15 from Schisandra plants sensitizes triple-negative breast cancer cells to lapatinib.".CANCER LETTERS 504.(2021):125-136

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