PPDPF Promotes the Development of Mutant KRAS-Driven Pancreatic Ductal Adenocarcinoma by Regulating the GEF Activity of SOS1

doi:10.1002/advs.202202448

	PPDPF Promotes the Development of Mutant KRAS-Driven Pancreatic Ductal Adenocarcinoma by Regulating the GEF Activity of SOS1
	Ni, Qian-Zhi 1,2; Zhu, Bing 1; Ji, Yan 1; Zheng, Qian-Wen3 ; Liang, Xin 1; Ma, Ning 4; Jiang, Hao 5; Zhang, Feng-Kun 1; Shang, Yu-Rong 1; Wang, Yi-Kang 1; Xu, Sheng 1; Zhang, Er-Bin 1; Yuan, Yan-Mei 1; Chen, Tian-Wei 1; Yin, Fen-Fen 1; Cao, Hui-Jun 1; Huang, Jing-Yi 1; Xia, Ji 1; Ding, Xu-Fen 1; Qiu, Xiao-Song3 ; Ding, Kai 1; Song, Chao 6; Zhou, Wen-Tao 6; Wu, Meng 7; Wang, Kang 2; Lui, Rui 8; Lin, Qiu 1; Chen, Wei 9; Li, Zhi-Gang 4; Cheng, Shu-Qun 2; Wang, Xiao-Fan 10; Xie, Dong1,3,11 ; Li, Jing-Jing 1
	2022-12-01
发表期刊	ADVANCED SCIENCE (IF:14.3[JCR-2023],16.3[5-Year])
EISSN	2198-3844
卷号	10 期号:2
发表状态	已发表
DOI	10.1002/advs.202202448
摘要	The guanine nucleotide exchange factor (GEF) SOS1 catalyzes the exchange of GDP for GTP on RAS. However, regulation of the GEF activity remains elusive. Here, the authors report that PPDPF functions as an important regulator of SOS1. The expression of PPDPF is significantly increased in pancreatic ductal adenocarcinoma (PDAC), associated with poor prognosis and recurrence of PDAC patients. Overexpression of PPDPF promotes PDAC cell growth in vitro and in vivo, while PPDPF knockout exerts opposite effects. Pancreatic-specific deletion of PPDPF profoundly inhibits tumor development in KRAS(G12D)-driven genetic mouse models of PDAC. PPDPF can bind GTP and transfer GTP to SOS1. Mutations of the GTP-binding sites severely impair the tumor-promoting effect of PPDPF. Consistently, mutations of the critical amino acids mediating SOS1-PPDPF interaction significantly impair the GEF activity of SOS1. Therefore, this study demonstrates a novel model of KRAS activation via PPDPF-SOS1 axis, and provides a promising therapeutic target for PDAC.
关键词	KRAS pancreatic ductal adenocarcinoma pancreatic progenitor cell differentiation proliferation factor SOS1
URL	查看原文
收录类别	SCI ; EI ; SCOPUS
语种	英语
资助项目	National Natural Science Foundation of China["82030084","81730083","82172950","81972757"] ; Youth Innovation Promotion Association of Chinese Academy of Sciences fund[2017324] ; China Postdoctoral Science Foundation Fund[2019661657]
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science
WOS类目	Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
WOS记录号	WOS:000892773300001
出版者	WILEY
EI入藏号	20225013222981
EI主题词	Tumors
EI分类号	461.2 Biological Materials and Tissue Engineering ; 461.6 Medicine and Pharmacology ; 461.9 Biology ; 801.2 Biochemistry
原始文献类型	Journal article (JA)
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/258939
专题	生命科学与技术学院_博士生生命科学与技术学院_特聘教授组_谢东组
通讯作者	Xie, Dong; Li, Jing-Jing
作者单位	1.Univ Chinese Acad Sci, Chinese Acad Sci, CAS Key Lab Nutr Metab & Food Safety, Shanghai Inst Nutr & Hlth, Shanghai 200031, Peoples R China 2.Naval Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Hepat Surg 6, Shanghai 200433, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 4.Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Dept Thorac Surg, Sect Esophageal Surg, Shanghai 200030, Peoples R China 5.Cent South Univ, Sch Life Sci, Dept Biomed Informat, Changsha 410013, Peoples R China 6.Fudan Univ, Zhongshan Hosp, Dept Pancreat Surg, Shanghai 200032, Peoples R China 7.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai 200031, Peoples R China 8.Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200438, Peoples R China 9.Tongde Hosp Zhejiang Prov, Canc Inst Integrated Tradit Chinese & Western Med, Hangzhou 310012, Zhejiang, Peoples R China 10.Duke Univ, Dept Pharmacol & Canc Biol, Med Ctr, Durham, NC 27710 USA 11.China Natl Ctr Food Safety Risk Assessment, NHC Key Lab Food Safety Risk Assessment, Beijing 100022, 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	Ni, Qian-Zhi,Zhu, Bing,Ji, Yan,et al. PPDPF Promotes the Development of Mutant KRAS-Driven Pancreatic Ductal Adenocarcinoma by Regulating the GEF Activity of SOS1[J]. ADVANCED SCIENCE,2022,10(2).
APA	Ni, Qian-Zhi.,Zhu, Bing.,Ji, Yan.,Zheng, Qian-Wen.,Liang, Xin.,...&Li, Jing-Jing.(2022).PPDPF Promotes the Development of Mutant KRAS-Driven Pancreatic Ductal Adenocarcinoma by Regulating the GEF Activity of SOS1.ADVANCED SCIENCE,10(2).
MLA	Ni, Qian-Zhi,et al."PPDPF Promotes the Development of Mutant KRAS-Driven Pancreatic Ductal Adenocarcinoma by Regulating the GEF Activity of SOS1".ADVANCED SCIENCE 10.2(2022).