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

doi:10.1016/j.canlet.2021.02.009

KIB OpenIR

	Targeting ubiquitin conjugating enzyme UbcH5b by a triterpenoid PC3-15 from Schisandra plants sensitizes triple-negative breast cancer cells to lapatinib
	Huang,Maobo ; Zhou,Yuanfei ; Duan,Dongzhu ; Yang,Chuanyu ; Zhou,Zhongmei ; Li,Fubing ; Kong,Yanjie ; Hsieh,Yi-Ching ; Zhang,Ruihan ; Ding,Wenping ; Xiao,Weilie ; Puno,PemaTenzin ; Chen,Ceshi
	2021
发表期刊	CANCER LETTERS
ISSN	0304-3835
卷号	504 页码:125-136
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.
关键词	HECTD3 UbcH5b Ubiquitination Autophagy Schisandraceae triterpenoid
DOI	10.1016/j.canlet.2021.02.009
WOS记录号	WOS:000625376500012
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/73765
专题	中国科学院昆明植物研究所
作者单位	1.Chinese Acad Sci & Yunnan Prov, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mech, Kunming, Yunnan, Peoples R China 2.Univ Chinese Acad Sci, Kunming Coll Life Sci, Kunming, Yunnan, Peoples R China 3.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 4.Baoji Univ Arts & Sci, Shaanxi Key Lab Phytochem, Baoji 721013, Peoples R China 5.Baoji Univ Arts & Sci, Coll Chem & Chem Engn, Baoji 721013, Peoples R China 6.Guangzhou Med Univ, Affiliated Canc Hosp & Inst, Guangzhou 510095, Peoples R China 7.Shenzhen Univ, Hlth Sci Ctr, Affiliated Hosp 1, Biobank,Shenzhen Peoples Hosp 2, Shenzhen 518035, Peoples R China 8.Albany Med Coll, Ctr Cell Biol & Canc Res, 47 New Scotland Ave, Albany, NY 12208 USA 9.Yunnan Univ, Sch Chem Sci & Technol, Minist Educ & Yunnan Prov,Key Lab Med Chemm Nat R, Key Lab Med Chem,State Key Lab Conservat & Utiliz, 2 North Cuihu Rd, Kunming 650091, Yunnan, Peoples R China 10.Chinese Acad Sci, Kunming Inst Zool, KIZ CUHK Joint Lab Bioresources & Mol Res Common, Kunming 650223, Yunnan, Peoples R 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.
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,504,125-136.
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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