Elevation of EIF4G1 Promotes Non-small Cell Lung Cancer Progression by Activating MTOR Signalling

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2021 Feb 1

PMID 33523588

Citations 8

Authors

Ying Lu

Shanshan Yu

Guangxue Wang

Zuan Ma

Xuelian Fu

Yueyu Cao

Qinchuan Li

Zengguang Xu

Affiliations

Soon will be listed here.

Abstract

Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1), as the key component of the transcription initiation factor complex EIF4F, is significantly upregulated in multiple solid tumours, including lung cancer. However, the function and mechanism of EIF4G1 in the regulation of non-small-cell lung cancer (NSCLC) remain unclear. Here, using the clinical samples and the comprehensive survival analysis platforms Kaplan-Meier plotter, we observed aberrant upregulation of EIF4G1 in NSCLC tissues; furthermore, high expression of EIF4G1 showed association with low differentiation of lung cancer cells and poor overall survival in NSCLC patients. Non-small-cell lung cancer cell line A549 and H1703 stably infected with EIF4G1 shRNA were used to determine the function of EIF4G1 in regulating cell proliferation and tumorigenesis in vitro and in vivo. The results demonstrated that EIF4G1 promoted the G1/S transition of the cell cycle and tumour cell proliferation in non-small cell lung cancer. Mechanistically, EIF4G1 was found to regulate the expression and phosphorylation of mTOR (Ser2448), which mediates the tumorigenesis-promoting function of EIF4G1. The inhibition of mTOR attenuated the EIF4G1-induced development and progression of tumours. These findings demonstrated that EIF4G1 is a new potential molecular target for the clinical treatment of non-small cell lung cancer.

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References

Cencic R, Hall D, Robert F, Du Y, Min J, Li L . Reversing chemoresistance by small molecule inhibition of the translation initiation complex eIF4F. Proc Natl Acad Sci U S A. 2010; 108(3):1046-51. PMC: 3024666. DOI: 10.1073/pnas.1011477108. View

Kim D, Sarbassov D, Ali S, Latek R, Guntur K, Erdjument-Bromage H . GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Mol Cell. 2003; 11(4):895-904. DOI: 10.1016/s1097-2765(03)00114-x. View

Feng Y, Pinkerton A, Hulea L, Zhang T, Davies M, Grotegut S . SBI-0640756 Attenuates the Growth of Clinically Unresponsive Melanomas by Disrupting the eIF4F Translation Initiation Complex. Cancer Res. 2015; 75(24):5211-8. PMC: 4681635. DOI: 10.1158/0008-5472.CAN-15-0885. View

Siegel R, Miller K, Jemal A . Cancer statistics, 2018. CA Cancer J Clin. 2018; 68(1):7-30. DOI: 10.3322/caac.21442. View

Riley T, Sontag E, Chen P, Levine A . Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol. 2008; 9(5):402-12. DOI: 10.1038/nrm2395. View

Silvera D, Arju R, Darvishian F, Levine P, Zolfaghari L, Goldberg J . Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer. Nat Cell Biol. 2009; 11(7):903-8. DOI: 10.1038/ncb1900. View

Liu J, Xia H, Kim M, Xu L, Li Y, Zhang L . Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13. Cell. 2011; 147(1):223-34. PMC: 3441147. DOI: 10.1016/j.cell.2011.08.037. View

Planchard D, Popat S, Kerr K, Novello S, Smit E, Faivre-Finn C . Correction to: "Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up". Ann Oncol. 2020; 30(5):863-870. DOI: 10.1093/annonc/mdy474. View

Moll U, Wolff S, Speidel D, Deppert W . Transcription-independent pro-apoptotic functions of p53. Curr Opin Cell Biol. 2005; 17(6):631-6. DOI: 10.1016/j.ceb.2005.09.007. View

10.

Boland J, Mansfield A, Roden A . Pulmonary sarcomatoid carcinoma-a new hope. Ann Oncol. 2017; 28(7):1417-1418. DOI: 10.1093/annonc/mdx276. View

11.

Ng T, Camidge D . Lung cancer's real adjuvant EGFR targeted therapy questions. Lancet Oncol. 2017; 19(1):15-17. DOI: 10.1016/S1470-2045(17)30875-6. View

12.

Yuan J, Luo K, Zhang L, Cheville J, Lou Z . USP10 regulates p53 localization and stability by deubiquitinating p53. Cell. 2010; 140(3):384-96. PMC: 2820153. DOI: 10.1016/j.cell.2009.12.032. View

13.

Jaiswal P, Koul S, Shanmugam P, Koul H . Eukaryotic Translation Initiation Factor 4 Gamma 1 (eIF4G1) is upregulated during Prostate cancer progression and modulates cell growth and metastasis. Sci Rep. 2018; 8(1):7459. PMC: 5945649. DOI: 10.1038/s41598-018-25798-7. View

14.

Lu Y, Yu S, Wang G, Ma Z, Fu X, Cao Y . Elevation of EIF4G1 promotes non-small cell lung cancer progression by activating mTOR signalling. J Cell Mol Med. 2021; 25(6):2994-3005. PMC: 7957198. DOI: 10.1111/jcmm.16340. View

15.

Keiper B, Gan W, Rhoads R . Protein synthesis initiation factor 4G. Int J Biochem Cell Biol. 1999; 31(1):37-41. DOI: 10.1016/s1357-2725(98)00130-7. View

16.

Prevot D, Darlix J, Ohlmann T . Conducting the initiation of protein synthesis: the role of eIF4G. Biol Cell. 2003; 95(3-4):141-56. DOI: 10.1016/s0248-4900(03)00031-5. View

17.

Rotow J, Bivona T . Understanding and targeting resistance mechanisms in NSCLC. Nat Rev Cancer. 2017; 17(11):637-658. DOI: 10.1038/nrc.2017.84. View

18.

Cao Y, Wei M, Li B, Liu Y, Lu Y, Tang Z . Functional role of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) in NSCLC. Oncotarget. 2016; 7(17):24242-51. PMC: 5029698. DOI: 10.18632/oncotarget.8168. View

19.

Chandrashekar D, Bashel B, Balasubramanya S, Creighton C, Ponce-Rodriguez I, Chakravarthi B . UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia. 2017; 19(8):649-658. PMC: 5516091. DOI: 10.1016/j.neo.2017.05.002. View

20.

Kaiser C, Dobrikova E, Bradrick S, Shveygert M, Herbert J, Gromeier M . Activation of cap-independent translation by variant eukaryotic initiation factor 4G in vivo. RNA. 2008; 14(10):2170-82. PMC: 2553731. DOI: 10.1261/rna.1171808. View