A synthetic peptide hijacks the catalytic subunit of class I PI3K to suppress the growth of cancer cells

doi:10.1016/j.canlet.2017.07.015

	A synthetic peptide hijacks the catalytic subunit of class I PI3K to suppress the growth of cancer cells
	Guo, Weiwei 1; You, Xue1,2 ; Wang, Xiao 1; Wang, Lin 1; Chen, Yan1,2
	2017-10
发表期刊	CANCER LETTERS (IF:9.1[JCR-2023],8.3[5-Year])
ISSN	0304-3835
卷号	405 页码:1-9
发表状态	已发表
DOI	10.1016/j.canlet.2017.07.015
摘要	Activation of class I Phosphoinositide 3-kinases (PI3Ks) by mutation or overexpression closely correlates with the development of various human cancers. Class I PI3Ks are heterodimers composed of p110 catalytic subunits and regulatory subunits represented by p85. PAQR3 has been found to inhibit p110 alpha activity by blocking its interaction with p85. In this study, we identified the N-terminal 6-55 amino acid residues of PAQR3 being sufficient for its interaction with p110 alpha. A synthetic peptide, P6-55, that contains the N-terminus of PAQR3 could disrupt the interactions of p110 alpha with both PAQR3 and p85. The activity of PI3K was also inhibited by P6-55, accompanied by significant inhibition of cancer cell proliferation. In a xenograft mouse model, P6-55 was able to reduce tumor growth in vivo. Furthermore, P6-55 was capable of inhibiting the elevated basal PI3K activity of H1047R, a hotspot mutation found in many types of human cancers. The cell proliferation and migration of cancer cells bearing H1047R mutation were also reduced by P6-55. In conclusion, our study provides a proof of concept that blocking the interaction of p110 alpha with p85 by a peptide can serve as a new strategy to inhibit the oncogenic activity of PI3K in cancer therapy. (C) 2017 Elsevier B.V. All rights reserved.
关键词	PI3K Peptide Therapy Gastric cancers Mouse model
收录类别	SCI
语种	英语
资助项目	Ministry of Science and Technology of China[2016YFA0500103]
WOS研究方向	Oncology
WOS类目	Oncology
WOS记录号	WOS:000412036200001
出版者	ELSEVIER IRELAND LTD
WOS关键词	PHOSPHOINOSITIDE 3-KINASE P110-ALPHA ; HEPATOCELLULAR-CARCINOMA ; TUMOR-SUPPRESSOR ; BREAST-CANCER ; PAQR3 PLAYS ; MUTATIONS ; PIK3CA ; TUMORIGENESIS ; RKTG ; PROGRESSION
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/9916
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_陈雁组生命科学与技术学院_博士生
通讯作者	Chen, Yan
作者单位	1.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai 200031, Peoples R China 2.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Guo, Weiwei,You, Xue,Wang, Xiao,et al. A synthetic peptide hijacks the catalytic subunit of class I PI3K to suppress the growth of cancer cells[J]. CANCER LETTERS,2017,405:1-9.
APA	Guo, Weiwei,You, Xue,Wang, Xiao,Wang, Lin,&Chen, Yan.(2017).A synthetic peptide hijacks the catalytic subunit of class I PI3K to suppress the growth of cancer cells.CANCER LETTERS,405,1-9.
MLA	Guo, Weiwei,et al."A synthetic peptide hijacks the catalytic subunit of class I PI3K to suppress the growth of cancer cells".CANCER LETTERS 405(2017):1-9.