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PPDPF Promotes the Development of Mutant KRAS-Driven Pancreatic Ductal Adenocarcinoma by Regulating the GEF Activity of SOS1.
Ni, Qian-Zhi; Zhu, Bing; Ji, Yan; Zheng, Qian-Wen; Liang, Xin; Ma, Ning; Jiang, Hao; Zhang, Feng-Kun; Shang, Yu-Rong; Wang, Yi-Kang; Xu, Sheng; Zhang, Er-Bin; Yuan, Yan-Mei; Chen, Tian-Wei; Yin, Fen-Fen; Cao, Hui-Jun; Huang, Jing-Yi; Xia, Ji; Ding, Xu-Fen; Qiu, Xiao-Song; Ding, Kai; Song, Chao; Zhou, Wen-Tao; Wu, Meng; Wang, Kang; Lui, Rui; Lin, Qiu; Chen, Wei; Li, Zhi-Gang; Cheng, Shu-Qun; Wang, Xiao-Fan; Xie, Dong; Li, Jing-Jing.
Afiliação
  • Ni QZ; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Zhu B; Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200433, P. R. China.
  • Ji Y; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Zheng QW; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Liang X; School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, P. R. China.
  • Ma N; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Jiang H; Department of Thoracic Surgery, Section of Esophageal Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, P. R. China.
  • Zhang FK; Department of Biomedical Informatics, School of Life Sciences, Central South University, Changsha, 410013, P. R. China.
  • Shang YR; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Wang YK; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Xu S; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Zhang EB; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Yuan YM; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Chen TW; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Yin FF; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Cao HJ; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Huang JY; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Xia J; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Ding XF; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Qiu XS; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Ding K; School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, P. R. China.
  • Song C; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Zhou WT; Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China.
  • Wu M; Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China.
  • Wang K; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Lui R; Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200433, P. R. China.
  • Lin Q; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, P. R. China.
  • Chen W; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • Li ZG; Cancer Institute of Integrated Traditional Chinese and Western Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, 310012, P. R. China.
  • Cheng SQ; Department of Thoracic Surgery, Section of Esophageal Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, P. R. China.
  • Wang XF; Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200433, P. R. China.
  • Xie D; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, 27710, USA.
  • Li JJ; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
Adv Sci (Weinh) ; 10(2): e2202448, 2023 01.
Article em En | MEDLINE | ID: mdl-36453576
ABSTRACT
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 KRASG12D -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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article