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Updated: Jan 3, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

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JNK-Dependent cJun Phosphorylation Mitigates TGFβ- and EGF-Induced Pre-Malignant Breast Cancer Cell Invasion by

Anders Sundqvist1, Oleksandr Voytyuk1, Mohamed Hamdi2,3

  • 1Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Box 582, SE-751 23 Uppsala, Sweden.

Cells
|November 27, 2019
PubMed

Insights

Jun N-terminal kinase (JNK) phosphorylation of cJun inhibits breast cancer cell invasion. This contrasts with MEK-AP-1 signaling, highlighting distinct pathways that regulate tumor progression and offer therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Transforming growth factor-β (TGFβ) exhibits dual roles in breast cancer, acting as both a tumor suppressor and promoter.
  • Smad proteins are key intracellular mediators of TGFβ signaling, forming complexes with other transcription factors.
  • Previous research linked activator protein (AP)-1 transcription factors (Jun/Fos) to TGFβ/epidermal growth factor (EGF)-induced breast cancer cell invasion and migration.

Purpose of the Study:

  • To investigate the role of Jun N-terminal kinase (JNK)-dependent cJun phosphorylation in regulating breast cancer cell invasion and migration.
  • To elucidate the distinct functions of MEK-AP-1 and JNK-phospho-cJun pathways in TGFβ-mediated responses.

Main Methods:

  • Utilized phospho-deficient, phospho-mimicking, and dimer-specific cJun mutants to analyze JNK's effect on cJun activity.
  • Employed a mutant version of the phosphatase MKP1 to specifically inhibit JNK activity.
  • Assessed the impact of cJun phosphorylation on the induction of Jun/Fos-regulated genes and on cell migration/invasion.

Main Results:

  • Hyper-phosphorylation of cJun by JNK significantly impaired its ability to induce target genes and promote cell migration and invasion.
  • MEK-AP-1 signaling was identified as pro-invasive, while JNK-dependent cJun phosphorylation demonstrated anti-invasive functions.
  • Differential regulation of Smad- and AP-1-dependent TGFβ target genes by these pathways was observed.

Conclusions:

  • JNK-mediated cJun phosphorylation acts as a negative regulator of breast cancer cell invasion and migration.
  • Distinct signaling pathways involving MEK-AP-1 and JNK-phospho-cJun have opposing effects on tumor invasiveness.
  • Findings provide insights for personalized cancer therapy, particularly for breast tumors with specific signaling pathway alterations (e.g., activated EGF receptor-Ras or inactivated JNK).
Keywords:
AP-1JNKMAPKTGFβcJuninvasionsignaling

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