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Article Open Access

AMPK decreases ERK1/2 activity and cancer cell sensitivity to nutrition deprivation by mediating a positive feedback loop involving eEF2K

  • Authors:
    • Shujuan Tong
    • Tao Zhou
    • Yufen Meng
    • Dongqin Xu
    • Jianping Chen
  • View Affiliations / Copyright

    Affiliations: Department of Pathogenic Biology and Immunology, School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
    Copyright: © Tong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 61-66
    |
    Published online on: April 21, 2020
       https://doi.org/10.3892/ol.2020.11554
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Abstract

Nutrition deprivation (ND) is a common feature of the tumor microenvironment. Tumor cells, therefore, frequently develop resistance mechanisms against ND. One of these mechanisms is the activation of the AMP‑activated protein kinase (AMPK), which promotes cell survival under ND. AMPK activation promotes the activity of eukaryotic elongation factor 2 kinase (eEF2K), thereby blocking protein synthesis. The results of the present study indicated the inhibiting effect of AMPK activation on mitogen‑activated protein kinase (ERK1/2) activity, which in turn downregulates G1/S transition and promotes cell survival by mediating eEF2K under ND. The knockdown of ERK1/2 enhances cancer cell survival under ND. In the presence of nutrients, eEF2k interacts with dual‑specificity mitogen‑activated protein kinase kinase (MEK)1/2, conferring a positive feedback loop via MEK1/2‑ERK1/2‑ribosomal protein S6 kinase α‑1‑eEF2K signaling, leading to the constitutive activation of ERK1/2. By contrast, under acute ND, AMPK activation blocked the interaction between eEF2K and MEK1/2, contributing to the increased resistance of cancer cells to ND. The present findings reveal a previously undiscovered mechanism that uses AMPK activation to mediate ERK1/2‑regulated protein synthesis and cell survival by inhibiting eEF2K‑MEK1/2 interaction under ND conditions.
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1 

Caro-Maldonado A and Muñoz-Pinedo C: Dying for something to eat: How cells respond to starvation. Open Cell Signal J. 3:42–51. 2011. View Article : Google Scholar

2 

Jeon SM, Chandel NS and Hay N: AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature. 485:661–665. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Hardie DG: Molecular pathways: Is AMPK a friend or a foe in cancer? Clin Cancer Res. 21:3836–3840. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Fu LL, Xie T, Zhang SY and Liu B: Eukaryotic elongation factor-2 kinase (eEF2K): A potential therapeutic target in cancer. Apoptosis. 19:1527–1531. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Johanns M, PyrDitRuys S, Houddane A, Vertommen D, Herinckx G, Hue L, Proud CG and Rider MH: Direct and indirect activation of eukaryotic elongation factor 2 kinase by AMP-activated protein kinase. Cell Signal. 36:212–221. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Meloche S and Pouysségur J: The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition. Oncogene. 26:3227–3239. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Lavoie JN, L'Allemain G, Brunet A, Muller R and Pouyssegur J: Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway. J Biol Chem. 271:20608–20616. 1996. View Article : Google Scholar : PubMed/NCBI

8 

Weinberg RA: The retinoblastoma protein and cell cycle control. Cell. 81:323–330. 1995. View Article : Google Scholar : PubMed/NCBI

9 

Bracken AP, Ciro M, Cocito A and Helin K: E2F target genes: Unraveling the biology. Trends Biochem Sci. 29:409–417. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Zi X and Agarwal R: Modulation of mitogen-activated protein kinase activation and cell cycle regulators by the potent skin cancer preventive agent silymarin. Biochem Biophys Res Commun. 263:528–536. 1999. View Article : Google Scholar : PubMed/NCBI

11 

Yuan HX, Xiong Y and Guan KL: Nutrient sensing, metabolism, and cell growth control. Mol Cell. 49:379–387. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Cagnol S and Chambard JC: ERK and cell death: Mechanisms of ERK-induced cell death-apoptosis, autophagy and senescence. FEBS J. 277:2–21. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Mebratu Y and Tesfaigzi Y: How ERK1/2 activation controls cell proliferation and cell death is subcellular localization the answer? Cell Cycle. 8:1168–1175. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Wang X, Li W, Williams M, Terada N, Alessi DR and Proud CG: Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase. EMBO J. 20:4370–4379. 2001. View Article : Google Scholar : PubMed/NCBI

15 

Leprivier G, Remke M, Rotblat B, Dubuc A, Mateo AR, Kool M, Agnihotri S, El-Naggar A, Yu B, Somasekharan SP, et al: The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation. Cell. 153:1064–1079. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Tang Q, Zhao S, Wu J, Zheng F, Yang L, Hu J and Hann SS: Inhibition of integrin-linked kinase expression by emodin through crosstalk of AMPKα and ERK1/2 signaling and reciprocal interplay of Sp1 and c-Jun. Cell Signal. 27:1469–1477. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Zheng F, Wu J, Zhao S, Luo Q, Tang Q, Yang L, Li L, Wu W and Hann SS: Baicalein increases the expression and reciprocal interplay of RUNX3 and FOXO3a through crosstalk of AMPKα and MEK/ERK1/2 signaling pathways in human non-small cell lung cancer cells. J Exp Clin Cancer Res. 34:412015. View Article : Google Scholar : PubMed/NCBI

18 

Browne GJ and Proud CG: A novel mTOR-regulated phosphorylation site in elongation factor 2 kinase modulates the activity of the kinase and its binding to calmodulin. Mol Cell Biol. 24:2986–2997. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Xie J, Mikolajek H, Pigott CR, Hooper KJ, Mellows T, Moore CE, Mohammed H, Werner JM, Thomas GJ and Proud CG: Molecular mechanism for the control of eukaryotic elongation factor 2 kinase by pH: Role in cancer cell survival. Mol Cell Biol. 35:1805–1824. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Tavares CD, Ferguson SB, Giles DH, Wang Q, Wellmann RM, O'Brien JP, Warthaka M, Brodbelt JS, Ren P and Dalby KN: The molecular mechanism of eukaryotic elongation factor 2 kinase activation. J Biol Chem. 289:23901–23916. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Browne GJ, Finn SG and Proud CG: Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, Serine 398. J Biol Chem. 279:12220–12231. 2004. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Tong S, Zhou T, Meng Y, Xu D and Chen J: AMPK decreases ERK1/2 activity and cancer cell sensitivity to nutrition deprivation by mediating a positive feedback loop involving eEF2K. Oncol Lett 20: 61-66, 2020.
APA
Tong, S., Zhou, T., Meng, Y., Xu, D., & Chen, J. (2020). AMPK decreases ERK1/2 activity and cancer cell sensitivity to nutrition deprivation by mediating a positive feedback loop involving eEF2K. Oncology Letters, 20, 61-66. https://doi.org/10.3892/ol.2020.11554
MLA
Tong, S., Zhou, T., Meng, Y., Xu, D., Chen, J."AMPK decreases ERK1/2 activity and cancer cell sensitivity to nutrition deprivation by mediating a positive feedback loop involving eEF2K". Oncology Letters 20.1 (2020): 61-66.
Chicago
Tong, S., Zhou, T., Meng, Y., Xu, D., Chen, J."AMPK decreases ERK1/2 activity and cancer cell sensitivity to nutrition deprivation by mediating a positive feedback loop involving eEF2K". Oncology Letters 20, no. 1 (2020): 61-66. https://doi.org/10.3892/ol.2020.11554
Copy and paste a formatted citation
x
Spandidos Publications style
Tong S, Zhou T, Meng Y, Xu D and Chen J: AMPK decreases ERK1/2 activity and cancer cell sensitivity to nutrition deprivation by mediating a positive feedback loop involving eEF2K. Oncol Lett 20: 61-66, 2020.
APA
Tong, S., Zhou, T., Meng, Y., Xu, D., & Chen, J. (2020). AMPK decreases ERK1/2 activity and cancer cell sensitivity to nutrition deprivation by mediating a positive feedback loop involving eEF2K. Oncology Letters, 20, 61-66. https://doi.org/10.3892/ol.2020.11554
MLA
Tong, S., Zhou, T., Meng, Y., Xu, D., Chen, J."AMPK decreases ERK1/2 activity and cancer cell sensitivity to nutrition deprivation by mediating a positive feedback loop involving eEF2K". Oncology Letters 20.1 (2020): 61-66.
Chicago
Tong, S., Zhou, T., Meng, Y., Xu, D., Chen, J."AMPK decreases ERK1/2 activity and cancer cell sensitivity to nutrition deprivation by mediating a positive feedback loop involving eEF2K". Oncology Letters 20, no. 1 (2020): 61-66. https://doi.org/10.3892/ol.2020.11554
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