Thyroid receptor-interacting protein 13 and EGFR form a feedforward loop promoting glioblastoma growth

doi:10.1016/j.canlet.2020.08.023

	Thyroid receptor-interacting protein 13 and EGFR form a feedforward loop promoting glioblastoma growth
	Hu, Lulu 1; Shen, Dachuan 5; Liang, Dapeng 1; Shi, Ji 4; Song, Chunyan 3; Jiang, Ke 1,2; Ren, Menglin 1; Du, Sha 1; Cheng, Wei 1; Ma, Jianmei 9
刊名	CANCER LETTERS
	2020-11-28
卷号	493
关键词	Glioblastoma (GBM) EGFR EGFRvIII TRIP13 Osimertinib
ISSN号	0304-3835
DOI	10.1016/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.
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关键词	TRIP13 AAA-ATPASE ; CHECKPOINT ; CANCER ; TUMORIGENESIS ; PROGRESSION ; ACTIVATION ; EXPRESSION ; RESISTANCE ; INHIBITORS
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
内容类型	期刊论文
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.Tongji Univ, Shanghai Peoples Hosp 10, Dept Med Oncol, Shanghai 200072, Peoples R China 3.Capital Med Univ, Beijing Tiantan Hosp, Neurosurg Ctr, Dept Neurooncol, 119 South Fourth Rang West Rd, Beijing 100070, Peoples R China 4.China Med Univ, Liaoning Canc Hosp & Inst, Dept Neurosurg, Canc Hosp, 44 Xiaoheyan Rd, Shenyang 110042, Peoples R China 5.Dalian Univ, Dept Oncol, Affiliated Zhongshan Hosp, Dalian, Peoples R China 6.Chinese Acad Sci, Ctr Med Phys & Technol, Hefei Inst Phys Sci, Hefei, Peoples R China 7.Trinity Coll Dublin, Dublin, Ireland 8.St James Hosp, Trinity Translat Med Inst, Thorac Oncol Res Grp, Trinity Ctr Hlth Sci, Dublin, Ireland 9.Dalian Med Univ, Coll Basic Med Sci, Dalian 116044, 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).