TY - JOUR
T1 - Cell-Type-Specific Chromatin States Differentially Prime Squamous Cell Carcinoma Tumor-Initiating Cells for Epithelial to Mesenchymal Transition
AU - Latil, Mathilde
AU - Nassar, Dany
AU - Beck, Benjamin
AU - Boumahdi, Soufiane
AU - Wang, Li
AU - Brisebarre, Audrey
AU - Dubois, Christine
AU - Nkusi, Erwin
AU - Lenglez, Sandrine
AU - Checinska, Agnieszka
AU - Vercauteren Drubbel, Alizée
AU - Devos, Michael
AU - Declercq, Wim
AU - Yi, Rui
AU - Blanpain, Cédric
N1 - Funding Information:
We thank Angela Nieto for her constructive comments on the manuscript. We thank the animal house facility from the ULB (Erasme campus). We thank Frederick Libert and Anne Lefort for their help with the RNA sequencing (ULB genomic core facility, Erasme campus). C.B. is an investigator of WELBIO. M.L. is supported by a long-term EMBO fellowship (ALTF 1172-2013), and D.N. is supported by the TELEVIE. This work was supported by the FNRS, TELEVIE, the ERC (ERC-2013-CoG/ Project #616333 Expand), the PAI program (P7/03-CanEpi), a research grant from the Worldwide Cancer Research (#15-0270), Fondation Contre le Cancer (Convention 2012-171), the ULB fondation, the fond Gaston Ithier, the foundation Bettencourt Schueller, and the Fondation Baillet Latour.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/2/2
Y1 - 2017/2/2
N2 - 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.
AB - 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.
KW - EMT
KW - cancer cell of origin
KW - cancer cell plasticity
KW - cellular reprogramming
KW - epigenetic
KW - gene regulatory network
KW - skin cancer
KW - transcription factors
KW - tumor heterogeneity
UR - http://www.scopus.com/inward/record.url?scp=85007268713&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85007268713&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2016.10.018
DO - 10.1016/j.stem.2016.10.018
M3 - Article
C2 - 27889319
AN - SCOPUS:85007268713
VL - 20
SP - 191-204.e5
JO - Cell Stem Cell
JF - Cell Stem Cell
SN - 1934-5909
IS - 2
ER -
