CLC number:
On-line Access: 2022-10-12
Received: 2022-03-18
Revision Accepted: 2022-06-02
Crosschecked: 2022-10-13
Cited: 0
Clicked: 874
Citations: Bibtex RefMan EndNote GB/T7714
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,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2200144 @article{title="UPF1 increases amino acid levels and promotes cell proliferation in lung adenocarcinoma via the eIF2α-ATF4 axis", %0 Journal Article TY - JOUR
UPF1通过调控eIF2α-ATF4通路提高细胞内氨基酸水平促进肺腺癌增殖1大连医科大学附属第一医院胸外科,大连市肺癌诊疗中心,中国大连,116011 2中国科学院分析化学分离科学重点实验室,中国科学院大连化学物理研究所,中国大连,116023 目的:UPF1是调节无义介导的mRNA降解的核心因子,参与多种肿瘤进展相关分子通路的调节,其在肺腺癌氨基酸代谢中的作用尚不清楚。 方法和结果:本研究通过结合生物信息学和代谢组学,分析发现UPF1与肺腺癌中部分氨基酸代谢通路显著相关,证实UPF1敲低后可显著抑制氨基酸代谢重编程核心蛋白ATF4的表达及eIF2α-Ser51位点的磷酸化水平,且UPF1通过调控ATF4蛋白增加肺腺癌细胞的氨基酸水平进而促进细胞增殖。在临床患者样本数据库中,肺腺癌组织中UPF1的mRNA水平表达异常,UPF1和ATF4均高表达的肺腺癌患者有着较差的总生存期。 结论:本研究表明,UPF1是肿瘤氨基酸代谢重编程的潜在调控因子,可作为肺腺癌治疗的新靶点。 关键词组: Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article
Reference[1]Abdel-WahabAF, MahmoudW, Al-HarizyRM, 2019. Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy. Pharmacol Res, 150:104511. [2]AdamsCM, 2007. Role of the transcription factor ATF4 in the anabolic actions of insulin and the anti-anabolic actions of glucocorticoids. J Biol Chem, 282(23):16744-16753. [3]AmeriK, HarrisAL, 2008. Activating transcription factor 4. Int J Biochem Cell Biol, 40(1):14-21. [4]BaiXP, NiJ, BeretovJ, et al., 2021. Activation of the eIF2α/ATF4 axis drives triple-negative breast cancer radioresistance by promoting glutathione biosynthesis. Redox Biol, 43:101993. [5]B’chirW, MaurinAC, CarraroV, et al., 2013. The eIF2α/ATF4 pathway is essential for stress-induced autophagy gene expression. Nucleic Acids Res, 41(16):7683-7699. [6]BoroughsLK, DeBerardinisRJ, 2015. Metabolic pathways promoting cancer cell survival and growth. Nat Cell Biol, 17(4):351-359. [7]CaoYH, 2019. Adipocyte and lipid metabolism in cancer drug resistance. J Clin Invest, 129(8):3006-3017. [8]ChangL, LiCC, GuoT, et al., 2016. The human RNA surveillance factor UPF1 regulates tumorigenesis by targeting Smad7 in hepatocellular carcinoma. J Exp Clin Cancer Res, 35:8. [9]ChenBL, WangHM, LinXS, et al., 2021. UPF1: a potential biomarker in human cancers. Front Biosci (Landmark Ed), 26(5):76-84. [10]ChenPH, CaiL, HuffmanK, et al., 2019. Metabolic diversity in human non-small cell lung cancer cells. Mol Cell, 76(5):838-851.e5. [11]DehecqM, DecourtyL, NamaneA, et al., 2018. Nonsense-mediated mRNA decay involves two distinct Upf1-bound complexes. EMBO J, 37(21):e99278. [12]DiasAS, AlmeidaCR, HelgueroLA, et al., 2019. Metabolic crosstalk in the breast cancer microenvironment. Eur J Cancer, 121:154-171. [13]FerlayJ, SoerjomataramI, DikshitR, et al., 2015. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer, 136(5):E359-E386. [14]GeorgoudakiAM, ProkopecKE, BouraVF, et al., 2016. Reprogramming tumor-associated macrophages by antibody targeting inhibits cancer progression and metastasis. Cell Rep, 15(9):2000-2011. [15]GuoX, WangAM, WangW, et al., 2021. HRD1 inhibits fatty acid oxidation and tumorigenesis by ubiquitinating CPT2 in triple-negative breast cancer. Mol Oncol, 15(2):642-656. [16]GwinnDM, LeeAG, Briones-Martin-Del-CampoM, et al., 2018. Oncogenic KRAS regulates amino acid homeostasis and asparagine biosynthesis via ATF4 and alters sensitivity to L-asparaginase. Cancer Cell, 33(1):91-107.E6. [17]HaiT, CurranT, 1991. Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity. Proc Natl Acad Sci USA, 88(9):3720-3724. [18]HanSH, CaoDD, ShaJ, et al., 2020. LncRNA ZFPM2-AS1 promotes lung adenocarcinoma progression by interacting with UPF1 to destabilize ZFPM2. Mol Oncol, 14(5):1074-1088. [19]HanahanD, WeinbergRA, 2011. Hallmarks of cancer: the next generation. Cell, 144(5):646-674. [20]KawauchiK, ArakiK, TobiumeK, et al., 2008. p53 regulates glucose metabolism through an IKK-NF-κB pathway and inhibits cell transformation. Nat Cell Biol, 10(5):611-618. [21]KrishnamoorthyGP, DavidsonNR, LeachSD, et al., 2019. EIF1AX and RAS mutations cooperate to drive thyroid tumorigenesis through ATF4 and c-MYC. Cancer Discov, 9(2):264-281. [22]KurosakiT, PoppMW, MaquatLE, 2019. Quality and quantity control of gene expression by nonsense-mediated mRNA decay. Nat Rev Mol Cell Biol, 20(7):406-420. [23]LeeJV, CarrerA, ShahS, et al., 2014. Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation. Cell Metab, 20(2):306-319. [24]LiXZ, YanXH, 2019. Sensors for the mTORC1 pathway regulated by amino acids. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(9):699-712. [25]LiL, GengY, FengR, et al., 2017. The human RNA surveillance factor UPF1 modulates gastric cancer progression by targeting long non-coding RNA MALAT1. Cell Physiol Biochem, 42(6):2194-2206. [26]LiZY, ZhangHF, 2016. Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression. Cell Mol Life Sci, 73(2):377-392. [27]LieuEL, NguyenT, RhyneS, et al., 2020. Amino acids in cancer. Exp Mol Med, 52(1):15-30. [28]LiuC, KaramR, ZhouYQ, et al., 2014. The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous carcinoma. Nat Med, 20(6):596-598. [29]Lykke-AndersenS, JensenTH, 2015. Nonsense-mediated mRNA decay: an intricate machinery that shapes transcriptomes. Nat Rev Mol Cell Biol, 16(11):665-677. [30]MossmannD, ParkS, HallMN, 2018. mTOR signalling and cellular metabolism are mutual determinants in cancer. Nat Rev Cancer, 18(12):744-757. [31]NewmanAC, MaddocksODK, 2017. One-carbon metabolism in cancer. Br J Cancer, 116(12):1499-1504. [32]NicholsonP, YepiskoposyanH, MetzeS, et al., 2010. Nonsense-mediated mRNA decay in human cells: mechanistic insights, functions beyond quality control and the double-life of NMD factors. Cell Mol Life Sci, 67(5):677-700. [33]PeiCL, FeiKL, YuanXY, et al., 2019. LncRNA DANCR aggravates the progression of ovarian cancer by downregulating UPF1. Eur Rev Med Pharmacol Sci, 23(24):10657-10663. [34]PengYY, YangH, LiS, 2021. The role of glycometabolic plasticity in cancer. Pathol Res Pract, 226:153595. [35]PoppMWL, MaquatLE, 2013. Organizing principles of mammalian nonsense-mediated mRNA decay. Annu Rev Genet, 47:139-165. [36]SneeggenM, GuadagnoNA, ProgidaC, 2020. Intracellular transport in cancer metabolic reprogramming. Front Cell Dev Biol, 8:597608. [37]SungH, FerlayJ, SiegelRL, et al., 2021. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 71(3):209-249. Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou
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