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

Shujuan Tong1, Tao Zhou1,2, Yufen Meng1

  • 1Department of Pathogenic Biology and Immunology, School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China.

Oncology Letters
|June 23, 2020
PubMed

Insights

AMP-activated protein kinase (AMPK) helps cancer cells survive nutrition deprivation (ND) by blocking protein synthesis. This study reveals AMPK inhibits eEF2K-MEK1/2 interaction, enhancing cancer cell resistance to ND.

Area of Science:

  • Molecular Biology
  • Cancer Cell Biology
  • Biochemistry

Background:

  • Nutrition deprivation (ND) is a common challenge in the tumor microenvironment.
  • Cancer cells develop resistance to ND, often involving AMP-activated protein kinase (AMPK) activation.
  • AMPK activation promotes cell survival under ND by regulating protein synthesis.

Purpose of the Study:

  • To elucidate the mechanism by which AMPK activation mediates cancer cell survival under ND.
  • To investigate the role of eukaryotic elongation factor 2 kinase (eEF2K) and mitogen-activated protein kinase (ERK1/2) in this process.
  • To identify novel therapeutic targets for overcoming cancer cell resistance to ND.

Main Methods:

  • Investigated the interplay between AMPK, eEF2K, and ERK1/2 signaling pathways.
  • Utilized knockdown experiments to assess the role of ERK1/2 in cancer cell survival.
  • Examined the interaction between eEF2K and MEK1/2 under nutrient-rich and nutrient-deprived conditions.

Main Results:

  • AMPK activation inhibits ERK1/2 activity, downregulating G1/S transition and promoting survival via eEF2K.
  • Knockdown of ERK1/2 enhances cancer cell survival under ND.
  • AMPK activation blocks the eEF2K-MEK1/2 interaction under ND, increasing cancer cell resistance.

Conclusions:

  • AMPK activation mediates cancer cell survival under ND by inhibiting the eEF2K-MEK1/2 interaction.
  • This mechanism involves the regulation of ERK1/2 activity and protein synthesis.
  • Findings reveal a novel pathway for enhancing cancer cell sensitivity to nutrient deprivation.
Keywords:
AMP-activated protein kinaseeukaryotic elongation factor 2 kinasenutrition deprivationpositive feedback loop

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