title: Cell-Type-Specific Chromatin States Differentially Prime Squamous Cell Carcinoma Tumor-Initiating Cells for Epithelial to Mesenchymal Transition.
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.
authors.affiliation: Université libre de Buxelles (ULB), Institut de recherche interdisciplinaire en biologie humaine et moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Latil
authors.affiliation: Université libre de Buxelles (ULB), Institut de recherche interdisciplinaire en biologie humaine et moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Dany
authors.initials: D
authors.lastname: Nassar
authors.affiliation: Université libre de Buxelles (ULB), Institut de recherche interdisciplinaire en biologie humaine et moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Beck
authors.affiliation: Université libre de Buxelles (ULB), Institut de recherche interdisciplinaire en biologie humaine et moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Soufiane
authors.initials: S
authors.lastname: Boumahdi
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Université libre de Buxelles (ULB), Institut de recherche interdisciplinaire en biologie humaine et moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Audrey
authors.initials: A
authors.lastname: Brisebarre
authors.affiliation: Université libre de Buxelles (ULB), Institut de recherche interdisciplinaire en biologie humaine et moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Dubois
authors.affiliation: Université libre de Buxelles (ULB), Institut de recherche interdisciplinaire en biologie humaine et moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Erwin
authors.initials: E
authors.lastname: Nkusi
authors.affiliation: Université libre de Buxelles (ULB), Institut de recherche interdisciplinaire en biologie humaine et moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lenglez
authors.affiliation: Université libre de Buxelles (ULB), Institut de recherche interdisciplinaire en biologie humaine et moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Checinska
authors.affiliation: Université libre de Buxelles (ULB), Institut de recherche interdisciplinaire en biologie humaine et moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Alizée
authors.initials: A
authors.lastname: Vercauteren Drubbel
authors.affiliation: VIB Inflammation Research Center, Technologiepark 927, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052 Ghent, Belgium.
authors.forename: Michael
authors.initials: M
authors.lastname: Devos
authors.affiliation: VIB Inflammation Research Center, Technologiepark 927, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052 Ghent, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Declercq
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Yi
authors.affiliation: 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.
authors.forename: Cédric
authors.initials: C
authors.lastname: Blanpain
mesh_terms: D000818:Animals; D001483:Base Sequence; D063646:Carcinogenesis / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics; D002843:Chromatin / Q000378:metabolism*; D002999:Clone Cells; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D057809:HEK293 Cells; D018859:Hair Follicle / Q000473:pathology; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010750:Phosphoproteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D010750:Phosphoproteins; D012097:Repressor Proteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse
keywords: EMT; cancer cell of origin; cancer cell plasticity; cellular reprogramming; epigenetic; gene regulatory network; skin cancer; transcription factors; tumor heterogeneity