Cell-Type-Specific Chromatin States Differentially Prime Squamous Cell Carcinoma Tumor-Initiating Cells for Epithelial to Mesenchymal Transition

Mathilde Latil, Dany Nassar, Benjamin Beck, Soufiane Boumahdi, Li Wang, Audrey Brisebarre, Christine Dubois, Erwin Nkusi, Sandrine Lenglez, Agnieszka Checinska, Alizée Vercauteren Drubbel, Michael Devos, Wim Declercq, Rui Yi, Cédric Blanpain*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

Epithelial to mesenchymal transition (EMT) in cancer cells has been associated with metastasis, stemness, and resistance to therapy. Some tumors undergo EMT while others do not, which may reflect intrinsic properties of their cell of origin. However, this possibility is largely unexplored. By targeting the same oncogenic mutations to discrete skin compartments, we show that cell-type-specific chromatin and transcriptional states differentially prime tumors to EMT. Squamous cell carcinomas (SCCs) derived from interfollicular epidermis (IFE) are generally well differentiated, while hair follicle (HF) stem cell-derived SCCs frequently exhibit EMT, efficiently form secondary tumors, and possess increased metastatic potential. Transcriptional and epigenomic profiling revealed that IFE and HF tumor-initiating cells possess distinct chromatin landscapes and gene regulatory networks associated with tumorigenesis and EMT that correlate with accessibility of key epithelial and EMT transcription factor binding sites. These findings highlight the importance of chromatin states and transcriptional priming in dictating tumor phenotypes and EMT.

Original languageEnglish (US)
Pages (from-to)191-204.e5
JournalCell stem cell
Volume20
Issue number2
DOIs
StatePublished - Feb 2 2017
Externally publishedYes

Keywords

  • EMT
  • cancer cell of origin
  • cancer cell plasticity
  • cellular reprogramming
  • epigenetic
  • gene regulatory network
  • skin cancer
  • transcription factors
  • tumor heterogeneity

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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