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

  • Published online on: April 21, 2020     https://doi.org/10.3892/ol.2020.11554
  • Pages: 61-66
  • Copyright: © Tong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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July 2020
Volume 20 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

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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