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JNK-dependent gene regulatory circuitry governs mesenchymal fate

Sanjeeb Kumar Sahu1, Angela Garding1, Neha Tiwari2

  • 1Institute of Molecular Biology (IMB), Mainz, Germany.

The EMBO Journal
|July 10, 2015
PubMed

Insights

The JNK pathway drives the progression of epithelial to mesenchymal transition (EMT) by reprogramming gene expression and chromatin. Novel transcription factors mediate these EMT changes in development and cancer metastasis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Epithelial to mesenchymal transition (EMT) is crucial for development and cancer metastasis.
  • The precise role of JNK signaling dynamics and its downstream transcriptional reprogramming in EMT remains unclear.

Purpose of the Study:

  • To elucidate the role of JNK signaling in EMT progression and identify downstream transcriptional regulators.
  • To investigate the function of JNK-induced transcription factors in maintaining mesenchymal identity during development and disease.

Main Methods:

  • Analysis of JNK signaling dynamics during EMT.
  • Genome-wide transcriptional profiling and chromatin state analysis.
  • Identification and functional characterization of JNK-induced transcription factors.

Main Results:

  • JNK signaling is essential for EMT progression, not initiation, by reprogramming EMT genes and altering chromatin.
  • Eight novel JNK-induced transcription factors were identified as crucial for EMT.
  • Three of these factors are highly expressed in invasive cancers, maintaining mesenchymal identity, and are involved in neuronal migration in vivo.

Conclusions:

  • JNK signaling plays a critical, time-dependent role in establishing the transcriptional landscape of mesenchymal cells.
  • Novel transcription factors mediating EMT responses in development and cancer have been uncovered.
Keywords:
EMTJNK signalinggene regulationmetastasistranscription factors

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