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Updated: Dec 5, 2025

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
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Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

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ERK3/MAPK6 is required for KRAS-mediated NSCLC tumorigenesis

Katarzyna Bogucka1, Federico Marini2,3, Sebastian Rosigkeit1

  • 1Cell Biology Unit, University Medical Center of the Johannes Gutenberg University Mainz, 55131, Mainz, Germany.

Cancer Gene Therapy
|October 18, 2020
PubMed

Insights

Extracellular signal-regulated kinase 3 (ERK3) is essential for KRAS-driven non-small cell lung cancer (NSCLC) progression. Inhibiting ERK3 kinase activity shows promise for treating KRAS G12C-mutated lung tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • KRAS mutations are common drivers in non-small cell lung cancer (NSCLC).
  • Targeting KRAS or its downstream pathways is crucial for NSCLC treatment.
  • ERK3, an atypical mitogen-activated protein kinase (MAPK), has an unclear role in cancer.

Purpose of the Study:

  • To investigate the role of ERK3 in KRAS-mediated NSCLC.
  • To determine if ERK3 is a potential therapeutic target in KRAS-driven NSCLC.

Main Methods:

  • Assessed ERK3 expression and activation in lung cancer patient samples.
  • Utilized cell culture models of KRAS G12C-transformed human bronchial epithelial cells.
  • Performed in vitro kinase assays and in vivo tumor growth studies in mouse models.
  • Investigated the effect of ERK3 loss on anchorage-independent growth.

Main Results:

  • ERK3 is highly expressed in lung cancers and activated by oncogenic KRAS.
  • Phosphorylation of ERK3 at serine 189 is elevated in lung adenocarcinomas.
  • Loss of ERK3 inhibits anchorage-independent growth of KRAS G12C cells.
  • ERK3 kinase activity is required for KRAS-driven oncogenesis in vitro and in vivo.

Conclusions:

  • ERK3 plays an obligatory role in the progression of KRAS-driven NSCLC.
  • ERK3 kinase inhibitors represent a potential therapeutic strategy for KRAS G12C-mutated NSCLC.

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