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

KIZ OpenIR > 科研部门 > 肿瘤生物学（陈策实）

	Targeting ubiquitin conjugating enzyme UbcH5b by a triterpenoid PC3-15 from Schisandra plants sensitizes triple-negative breast cancer cells to lapatinib
	Huang, MB; Zhou, YF; Duan, DZ; Yang, CY; Zhou, ZM; Li, FB; Kong, YJ; Hsieh, YC; Zhang, RH; Ding, WP; Xiao, WL; Puno, P; Chen, CS
	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.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13681
专题	科研部门_肿瘤生物学（陈策实）
推荐引用方式 GB/T 7714	Huang, MB,Zhou, YF,Duan, DZ,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, MB.,Zhou, YF.,Duan, DZ.,Yang, CY.,Zhou, ZM.,...&Chen, CS.(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, MB,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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2023032928.pdf（9762KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文