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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

Methionyl-tRNA synthetase overexpression is associated with poor clinical outcomes in non-small cell lung cancer

Authors: Eun Young Kim, Ji Ye Jung, Arum Kim, Kwangsoo Kim, Yoon Soo Chang

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

Methionyl-tRNA synthetase (MRS) plays a critical role in initiating translation by transferring Met to the initiator tRNA (tRNAi Met) and protection against ROS-mediated damage, suggesting that its overexpression is related to cancer growth and drug resistance. In this study, the clinical implication of MRS expression in non-small cell lung cancer (NSCLC) was evaluated.

Methods

Immunoblot and immunohistochemical (IHC) analyses were performed using tissue lysates and formalin-fixed paraffin embedded (FFPE) tissue blocks from wild type C57BL/6, LSL-Kras G12D, and LSL-Kras G12D:p53fl/fl mice. For human studies, 12 paired adjacent normal appearing lung tissue lysates and cancer tissue lysates, in addition to 231 FFPE tissue samples, were used.

Results

MRS was weakly expressed in the spleen and intestinal epithelium and only marginally expressed in the kidney, liver, and lungs of wild type C57BL/6 mice. On the other hand, MRS was strongly expressed in the neoplastic region of lung tissue from LSL-Kras G12D and LSL-Kras G12D:p53fl/fl mice. Immunoblot analysis of the human normal appearing adjacent and lung cancer paired tissue lysates revealed cancer-specific MRS overexpression, which was related to mTORC1 activity. IHC analysis of the 231 FFPE lung cancer tissue samples showed that MRS expression was frequently detected in the cytoplasm of lung cancer cells (179 out of 231, 77.4%), with a small proportion (73 out of 231, 31.6%) also showing nuclear expression. The proportion of cases with positive MRS expression was higher in the advanced pStage subgroup (P = 0.018, χ2-test) and cases with MRS expression also had shorter DFS (161.6 vs 142.3, P = 0.014, log-rank test).

Conclusions

Taken together, MRS is frequently overexpressed in NSCLC. Moreover, MRS is related to mTORC1 activity and its overexpression is associated with poor clinical outcomes, indicating that it has potential as a putative therapeutic target.
Appendix
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Literature
1.
2.
DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64(4):252–71.CrossRefPubMed
3.
Aberle DR, Berg CD, Black WC, Church TR, Fagerstrom RM, Galen B, et al. The National Lung Screening Trial: overview and study design. Radiology. 2011;258(1):243–53.CrossRefPubMed
4.
Aberle DR, Abtin F, Brown K. Computed tomography screening for lung cancer: has it finally arrived? Implications of the national lung screening trial. J Clin Oncol. 2013;31(8):1002–8.CrossRefPubMedPubMedCentral
5.
I H, Cho JY: Lung Cancer Biomarkers. Adv Clin Chem 2015, 72:107-170.
6.
Kikuchi T, Carbone DP. Proteomics analysis in lung cancer: challenges and opportunities. Respirology (Carlton, Vic). 2007;12(1):22–8.CrossRef
7.
Han JM, Jeong SJ, Park MC, Kim G, Kwon NH, Kim HK, et al. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell. 2012;149(2):410–24.CrossRefPubMed
8.
Kim S, You S, Hwang D. Aminoacyl-tRNA synthetases and tumorigenesis: more than housekeeping. Nat Rev Cancer. 2011;11(10):708–18.CrossRefPubMed
9.
Ghanipour A, Jirstrom K, Ponten F, Glimelius B, Pahlman L, Birgisson H. The prognostic significance of tryptophanyl-tRNA synthetase in colorectal cancer. Cancer Epidemiol Biomark Prev. 2009;18(11):2949–56.CrossRef
10.
Wakasugi K, Slike BM, Hood J, Ewalt KL, Cheresh DA, Schimmel P. Induction of angiogenesis by a fragment of human tyrosyl-tRNA synthetase. J Biol Chem. 2002;277(23):20124–6.CrossRefPubMed
11.
Greenberg Y, King M, Kiosses WB, Ewalt K, Yang X, Schimmel P, et al. The novel fragment of tyrosyl tRNA synthetase, mini-TyrRS, is secreted to induce an angiogenic response in endothelial cells. FASEB J. 2008;22(5):1597–605.CrossRefPubMed
12.
Ray PS, Jia J, Yao P, Majumder M, Hatzoglou M, Fox PL. A stress-responsive RNA switch regulates VEGFA expression. Nature. 2009;457(7231):915–9.CrossRefPubMed
13.
Levy C, Fisher DE. Dual roles of lineage restricted transcription factors: the case of MITF in melanocytes. Transcription. 2011;2(1):19–22.CrossRefPubMed
14.
Ko YG, Kim EY, Kim T, Park H, Park HS, Choi EJ, et al. Glutamine-dependent antiapoptotic interaction of human glutaminyl-tRNA synthetase with apoptosis signal-regulating kinase 1. J Biol Chem. 2001;276(8):6030–6.CrossRefPubMed
15.
Kwon NH, Kang T, Lee JY, Kim HH, Kim HR, Hong J, et al. Dual role of methionyl-tRNA synthetase in the regulation of translation and tumor suppressor activity of aminoacyl-tRNA synthetase-interacting multifunctional protein-3. Proc Natl Acad Sci U S A. 2011;108(49):19635–40.CrossRefPubMedPubMedCentral
16.
Yannay-Cohen N, Carmi-Levy I, Kay G, Yang CM, Han JM, Kemeny DM, et al. LysRS serves as a key signaling molecule in the immune response by regulating gene expression. Mol Cell. 2009;34(5):603–11.CrossRefPubMed
17.
18.
Wolfson RL, Chantranupong L, Saxton RA, Shen K, Scaria SM, Cantor JR, et al. Sestrin2 is a leucine sensor for the mTORC1 pathway. Science. 2016;351(6268):43–8.CrossRefPubMed
19.
Hyun YS, Park HJ, Heo SH, Yoon BR, Nam SH, Kim SB, et al. Rare variants in methionyl- and tyrosyl-tRNA synthetase genes in late-onset autosomal dominant Charcot-Marie-tooth neuropathy. Clin Genet. 2014;86(6):592–4.CrossRefPubMed
20.
Park SG, Choi EC, Kim S. Aminoacyl-tRNA synthetase-interacting multifunctional proteins (AIMPs): a triad for cellular homeostasis. IUBMB Life. 2010;62(4):296–302.PubMed
Metadata
Title
Methionyl-tRNA synthetase overexpression is associated with poor clinical outcomes in non-small cell lung cancer
Authors
Eun Young Kim
Ji Ye Jung
Arum Kim
Kwangsoo Kim
Yoon Soo Chang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3452-9

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