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On-line Access: 2022-10-12

Received: 2022-03-18

Revision Accepted: 2022-06-02

Crosschecked: 2022-10-13

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Citations:  Bibtex RefMan EndNote GB/T7714


Hailong PIAO


Chundong GU


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Journal of Zhejiang University SCIENCE B 2022 Vol.23 No.10 P.863-875


UPF1 increases amino acid levels and promotes cell proliferation in lung adenocarcinoma via the eIF2α-ATF4 axis

Author(s):  Lei FANG, Huan QI, Peng WANG, Shiqing WANG, Tianjiao LI, Tian XIA, Hailong PIAO, Chundong GU

Affiliation(s):  Department of Thoracic Surgery, Lung Cancer Diagnosis and Treatment Center of Dalian, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China; more

Corresponding email(s):   guchundong@dmu.edu.cn, hpiao@dicp.ac.cn

Key Words:  Up-frameshift 1 (UPF1), Activating transcription factor 4 (ATF4), Amino acid metabolism, Lung adenocarcinoma

Lei FANG, Huan QI, Peng WANG, Shiqing WANG, Tianjiao LI, Tian XIA, Hailong PIAO, Chundong GU. UPF1 increases amino acid levels and promotes cell proliferation in lung adenocarcinoma via the eIF2α-ATF4 axis[J]. Journal of Zhejiang University Science B, 2022, 23(10): 863-875.

@article{title="UPF1 increases amino acid levels and promotes cell proliferation in lung adenocarcinoma via the eIF2α-ATF4 axis",
author="Lei FANG, Huan QI, Peng WANG, Shiqing WANG, Tianjiao LI, Tian XIA, Hailong PIAO, Chundong GU",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T UPF1 increases amino acid levels and promotes cell proliferation in lung adenocarcinoma via the eIF2α-ATF4 axis
%A Huan QI
%A Peng WANG
%A Shiqing WANG
%A Tianjiao LI
%A Tian XIA
%A Hailong PIAO
%A Chundong GU
%J Journal of Zhejiang University SCIENCE B
%V 23
%N 10
%P 863-875
%@ 1673-1581
%D 2022
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2200144

T1 - UPF1 increases amino acid levels and promotes cell proliferation in lung adenocarcinoma via the eIF2α-ATF4 axis
A1 - Lei FANG
A1 - Huan QI
A1 - Peng WANG
A1 - Shiqing WANG
A1 - Tianjiao LI
A1 - Tian XIA
A1 - Hailong PIAO
A1 - Chundong GU
J0 - Journal of Zhejiang University Science B
VL - 23
IS - 10
SP - 863
EP - 875
%@ 1673-1581
Y1 - 2022
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2200144

up-frameshift 1 (UPF1), as the most critical factor in nonsense-mediated messenger RNA (mRNA) decay (NMD), regulates tumor-associated molecular pathways in many cancers. However, the role of UPF1 in lung adenocarcinoma (LUAD) amino acid metabolism remains largely unknown. In this study, we found that UPF1 was significantly correlated with a portion of amino acid metabolic pathways in LUAD by integrating bioinformatics and metabolomics. We further confirmed that UPF1 knockdown inhibited activating transcription factor 4 (ATF4) and Ser51 phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), the core proteins in amino acid metabolism reprogramming. In addition, UPF1 promotes cell proliferation by increasing the amino-acid levels of LUAD cells, which depends on the function of ATF4. Clinically, UPF1 mRNA expression is abnormal in LUAD tissues, and higher expression of UPF1 and ATF4 was significantly correlated with poor overall survival (OS) in LUAD patients. Our findings reveal that UPF1 is a potential regulator of tumor-associated amino acid metabolism and may be a therapeutic target for LUAD.




Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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