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Cell Stem Cell. 2017 Feb 2;20(2):191-204.e5. doi: 10.1016/j.stem.2016.10.018. Epub 2016 Nov 23.

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

Author information

1
Université libre de Buxelles (ULB), Institut de recherche interdisciplinaire en biologie humaine et moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium.
2
Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA.
3
VIB Inflammation Research Center, Technologiepark 927, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052 Ghent, Belgium.
4
Université libre de Buxelles (ULB), Institut de recherche interdisciplinaire en biologie humaine et moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium; WELBIO, Université Libre de Bruxelles (ULB), 1070 Bruxelles, Belgium. Electronic address: cedric.blanpain@ulb.ac.be.

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.

KEYWORDS:

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

PMID:
27889319
PMCID:
PMC5939571
DOI:
10.1016/j.stem.2016.10.018
[Indexed for MEDLINE]
Free PMC Article

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