Twist1 induces distinct cell states depending on TGFBR1-activation

Diana Dragoi, Anja Krattenmacher, Vivek K. Mishra, Johanna M. Schmidt, Uwe J. Kloos, Lisa K. Meixner, Stefanie M. Hauck, Felix Buggenthin, Dennis Schwartz, Carsten Marr, Steven A. Johnsen, Christina H. Scheel

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Basic helix-loop-helix transcription factor Twist1 is a master regulator of Epithelial-Mesenchymal Transition (EMT), a cellular program implicated in different stages of development as well as metastatic dissemination of carcinomas. Here, we show that Twist1 requires TGF-beta type-I receptor (TGFBR1)-activation to bind an enhancer region of downstream effector ZEB1, thereby inducing ZEB1 transcription and EMT. When TGFBR1-phosphorylation is inhibited, Twist1 generates a distinct cell state characterized by collective invasion, simultaneous proliferation and expression of endothelial markers. By contrast, TGFBR1-activation directs Twist1 to induce stable mesenchymal transdifferentiation through EMT, thereby generating cells that display single-cell invasion, but lose their proliferative capacity. In conclusion, preventing Twist1-induced EMT by inhibiting TGFβ-signaling does not generally block acquisition of invasion, but switches mode from single-cell/non-proliferative to collective/proliferative. Together, these data reveal that transient Twist1-activation induces distinct cell states depending on signaling context and caution against the use of TGFβ-inhibitors as a therapeutic strategy to target invasiveness.

Original languageEnglish (US)
Pages (from-to)30396-30407
Number of pages12
Issue number21
StatePublished - May 24 2016


  • Breast cancer
  • Context dependence
  • Epithelial-mesenchymal transition
  • TGFBR1
  • Twist1

ASJC Scopus subject areas

  • Oncology


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