JNK-dependent gene regulatory circuitry governs mesenchymal fate

Sanjeeb Kumar Sahu, Angela Garding, N. Tiwari, Sudhir Thakurela, Joern Toedling, Susanne Gebhard, Felipe Ortega, Nikolai Schmarowski, Benedikt Berninger, Robert Nitsch, Marcus Schmidt, Vijay K Tiwari

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

The epithelial to mesenchymal transition (EMT) is a biological process in which cells lose cell-cell contacts and become motile. EMT is used during development, for example, in triggering neural crest migration, and in cancer metastasis. Despite progress, the dynamics of JNK signaling, its role in genomewide transcriptional reprogramming, and involved downstream effectors during EMT remain largely unknown. Here, we show that JNK is not required for initiation, but progression of phenotypic changes associated with EMT. Such dependency resulted from JNK-driven transcriptional reprogramming of critical EMT genes and involved changes in their chromatin state. Furthermore, we identified eight novel JNK-induced transcription factors that were required for proper EMT. Three of these factors were also highly expressed in invasive cancer cells where they function in gene regulation to maintain mesenchymal identity. These factors were also induced during neuronal development and function in neuronal migration in vivo. These comprehensive findings uncovered a kinetically distinct role for the JNK pathway in defining the transcriptome that underlies mesenchymal identity and revealed novel transcription factors that mediate these responses during development and disease.
Original languageEnglish
Pages (from-to)2162-2181
Number of pages20
JournalThe EMBO Journal
Volume34
Issue number16
DOIs
Publication statusPublished - 13 Aug 2015

Keywords

  • emt
  • gene regulation
  • jnk signaling
  • metastasis
  • transcription

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