title: SOX2 Is the Determining Oncogenic Switch in Promoting Lung Squamous Cell Carcinoma from Different Cells of Origin.
abstract: Lung squamous cell carcinoma (LSCC) is a devastating malignancy with no effective treatments, due to its complex genomic profile. Therefore, preclinical models mimicking its salient features are urgently needed. Here we describe mouse models bearing various combinations of genetic lesions predominantly found in human LSCC. We show that SOX2 but not FGFR1 overexpression in tracheobronchial basal cells combined with Cdkn2ab and Pten loss results in LSCC closely resembling the human counterpart. Interestingly, Sox2;Pten;Cdkn2ab mice develop LSCC with a more peripheral location when Club or Alveolar type 2 (AT2) cells are targeted. Our model highlights the essential role of SOX2 in commanding the squamous cell fate from different cells of origin and represents an invaluable tool for developing better intervention strategies.
authors.affiliation: Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
authors.forename: Giustina
authors.initials: G
authors.lastname: Ferone
authors.affiliation: Division of Experimental Animal Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
authors.forename: Ji-Ying
authors.initials: JY
authors.lastname: Song
authors.affiliation: ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Kate D
authors.initials: KD
authors.lastname: Sutherland
authors.affiliation: Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Skolkovo Institute of Science and Technology, Skolkovo Innovation Center, Building 5, Moscow 143026, Russia.
authors.forename: Rajith
authors.initials: R
authors.lastname: Bhaskaran
authors.affiliation: Division of Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: Monkhorst
authors.affiliation: Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
authors.forename: Jan-Paul
authors.initials: JP
authors.lastname: Lambooij
authors.affiliation: Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
authors.forename: Natalie
authors.initials: N
authors.lastname: Proost
authors.affiliation: Department of Molecular Oncology, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13092 Berlin, Germany.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Gargiulo
authors.affiliation: Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Skolkovo Institute of Science and Technology, Skolkovo Innovation Center, Building 5, Moscow 143026, Russia. Electronic address: a.berns@nki.nl.
authors.forename: Anton
authors.initials: A
authors.lastname: Berns
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000235:genetics; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000096:biosynthesis / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D059016:Tumor Microenvironment
chemical_list: C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1