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Updated: Oct 27, 2025

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline
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The MEK5/ERK5 Pathway in Health and Disease

Rupesh Paudel1, Lorenza Fusi1, Marc Schmidt1

  • 1Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, 97080 Würzburg, Germany.

International Journal of Molecular Sciences
|July 24, 2021
PubMed

Insights

The MEK5/ERK5 pathway protects tissues from mechanical stress and aids survival. However, it also promotes cancer cell survival and drug resistance, suggesting it as a therapeutic target.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The MEK5/ERK5 pathway is a mitogen-activated protein kinase (MAPK) cascade.
  • It responds to mitogens and various stress stimuli like cytokines, fluid shear stress, high osmolarity, and oxidative stress.
  • Physiologically, it functions as a mechanoreceptive pathway in the endothelium, mediating vasoprotective effects of laminar blood flow and maintaining tissue integrity in bone, cartilage, and muscle.

Purpose of the Study:

  • To highlight the significance of the MEK5/ERK5 pathway in both health and disease.
  • To focus on its protective role in healthy tissues under mechanical stress.
  • To examine its function as a therapy resistance pathway in cancers.

Main Methods:

  • Literature review and synthesis of existing research on the MEK5/ERK5 pathway.
  • Analysis of the pathway's involvement in physiological processes and disease states.
  • Discussion of therapeutic targeting strategies for cancer.

Main Results:

  • The MEK5/ERK5 pathway is crucial for survival and differentiation in mechanically stressed tissues.
  • In cancer, it acts as a significant escape mechanism, supporting tumor cell survival and proliferation under drug treatment.
  • Dysfunction of this pathway is linked to cardiovascular diseases like atherosclerosis.

Conclusions:

  • The MEK5/ERK5 pathway plays a dual role: protective in healthy tissues and promoting resistance in cancer.
  • Targeting this cascade presents a potential therapeutic strategy for cancer treatment.
  • Careful consideration of its protective stress response functions is necessary when developing therapies.
Keywords:
Krüppel-like factoratherosclerosisbonecartilageendotheliumextracellular-regulated kinase 5mechanotransductionmitogen-activated protein kinasestress signalingtumor

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