中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Thyroid receptor-interacting protein 13 and EGFR form a feedforward loop promoting glioblastoma growth

文献类型:期刊论文

作者Hu, Lulu1; Shen, Dachuan2; Liang, Dapeng1; Shi, Ji3; Song, Chunyan4; Jiang, Ke1,5; Ren, Menglin1; Du, Sha1; Cheng, Wei1; Ma, Jianmei6
刊名CANCER LETTERS
出版日期2020-11-28
卷号493
ISSN号0304-3835
关键词Glioblastoma (GBM) EGFR EGFRvIII TRIP13 Osimertinib
DOI10.1016/j.canlet.2020.08.023
通讯作者Xu, Qing(xuqingmd@aliyun.com) ; Li, Wenbin(liwenbin@ccmu.edu.cn) ; Piao, Haozhe(piaohaozhe@cancerhosp-ln-cmu.com) ; Meng, Songshu(ssmeng@dmu.edu.cn)
英文摘要Epidermal growth factor receptor (EGFR) amplification and EGFRvIII mutation drive glioblastoma (GBM) pathogenesis, but their regulation remains elusive. Here we characterized the EGFR/EGFRvIII "interactome" in GBM and identified thyroid receptor-interacting protein 13 (TRIP13), an AAA + ATPase, as an EGFR/EGFRvIII-associated protein independent of its ATPase activity. Functionally, TRIP13 augmented EGFR pathway activation and contributed to EGFR/EGFRvIII-driven GBM growth in GBM spheroids and orthotopic GBM xenograft models. Mechanistically, TRIP13 enhanced EGFR protein abundance in part by preventing Cbl-mediated ubiquitination and proteasomal degradation. Reciprocally, TRIP13 was phosphorylated at tyrosine(Y) 56 by EGFRvIII and EGF-activated EGFR. Abrogating TRIP13 Y56 phosphorylation dramatically attenuated TRIP13 expression-enhanced EGFR signaling and GBM cell growth. Clinically, TRIP13 expression was upregulated in GBM specimens and associated with poor patient outcome. In GBM, TRIP13 localized to cell membrane and cytoplasma and exhibited oncogenic effects in vitro and in vivo, depending on EGFR signaling but not the TRIP13 ATPase activity. Collectively, our findings uncover that TRIP13 and EGFR form a feedforward loop to potentiate EGFR signaling in GBM growth and identify a previously unrecognized ATPase activity-independent mode of action of TRIP13 in GBM biology.
WOS关键词TRIP13 AAA-ATPASE ; CHECKPOINT ; CANCER ; TUMORIGENESIS ; PROGRESSION ; ACTIVATION ; EXPRESSION ; RESISTANCE ; INHIBITORS
资助项目National Natural Science Foundation of China[81572707] ; National Natural Science Foundation of China[81772973] ; National Natural Science Foundation of China[81972338] ; National Natural Science Foundation of China[81402071] ; Clinical Capability Construction Project for Liaoning Provincial Hospitals[LNCCC-B04-2015] ; Key Project of Shanghai Health and Family Planning Commission[201640020]
WOS研究方向Oncology
语种英语
出版者ELSEVIER IRELAND LTD
WOS记录号WOS:000581522200019
资助机构National Natural Science Foundation of China ; Clinical Capability Construction Project for Liaoning Provincial Hospitals ; Key Project of Shanghai Health and Family Planning Commission
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/104573]  
专题中国科学院合肥物质科学研究院
通讯作者Xu, Qing; Li, Wenbin; Piao, Haozhe; Meng, Songshu
作者单位1.Dalian Med Univ, Inst Canc Stem Cell, 9 West Sect,South Lvshun Rd, Dalian 116044, Peoples R China
2.Dalian Univ, Dept Oncol, Affiliated Zhongshan Hosp, Dalian, Peoples R China
3.China Med Univ, Liaoning Canc Hosp & Inst, Dept Neurosurg, Canc Hosp, 44 Xiaoheyan Rd, Shenyang 110042, Peoples R China
4.Capital Med Univ, Beijing Tiantan Hosp, Neurosurg Ctr, Dept Neurooncol, 119 South Fourth Rang West Rd, Beijing 100070, Peoples R China
5.Tongji Univ, Shanghai Peoples Hosp 10, Dept Med Oncol, Shanghai 200072, Peoples R China
6.Dalian Med Univ, Coll Basic Med Sci, Dalian 116044, Peoples R China
7.St James Hosp, Trinity Translat Med Inst, Thorac Oncol Res Grp, Trinity Ctr Hlth Sci, Dublin, Ireland
8.Trinity Coll Dublin, Dublin, Ireland
9.Chinese Acad Sci, Ctr Med Phys & Technol, Hefei Inst Phys Sci, Hefei, Peoples R China
推荐引用方式
GB/T 7714
Hu, Lulu,Shen, Dachuan,Liang, Dapeng,et al. Thyroid receptor-interacting protein 13 and EGFR form a feedforward loop promoting glioblastoma growth[J]. CANCER LETTERS,2020,493.
APA Hu, Lulu.,Shen, Dachuan.,Liang, Dapeng.,Shi, Ji.,Song, Chunyan.,...&Meng, Songshu.(2020).Thyroid receptor-interacting protein 13 and EGFR form a feedforward loop promoting glioblastoma growth.CANCER LETTERS,493.
MLA Hu, Lulu,et al."Thyroid receptor-interacting protein 13 and EGFR form a feedforward loop promoting glioblastoma growth".CANCER LETTERS 493(2020).

入库方式: OAI收割

来源:合肥物质科学研究院

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