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

Autor: Rui Yi, Audrey Brisebarre, Agnieszka Checinska, Alizée Vercauteren Drubbel, Erwin Nkusi, Soufiane Boumahdi, Sandrine Lenglez, Christine Dubois, Michael Devos, Benjamin Beck, Mathilde Latil, Cédric Blanpain, Li Wang, Dany Nassar, Wim Declercq
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Skin Neoplasms
Transcription
Genetic
Carcinogenesis
Cellular differentiation
gene regulatory network
medicine.disease_cause
cancer cell of origin
Epigenesis
Genetic
Mice
cellular reprogramming
tumor heterogeneity
cancer cell plasticity
Neoplasm Metastasis
Epigenomics
skin cancer
EMT
Cell Differentiation
Sciences bio-médicales et agricoles
Chromatin
Editorial
embryonic structures
Carcinoma
Squamous Cell
Neoplastic Stem Cells
Molecular Medicine
Hair Follicle
epigenetic
Epithelial-Mesenchymal Transition
Biology
03 medical and health sciences
transcription factors
Genetics
medicine
Animals
Humans
Cell Lineage
Epithelial–mesenchymal transition
Epigenetics
Transcription factor
Base Sequence
Epithelial Cells
Cell Biology
Phosphoproteins
Clone Cells
Repressor Proteins
030104 developmental biology
HEK293 Cells
Cancer cell
Immunology
Cancer research
Trans-Activators
Zdroj: Cell stem cell, 20 (2
Popis: 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.
SCOPUS: ar.j
info:eu-repo/semantics/published
Databáze: OpenAIRE
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