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SOX2 is the determining oncogenic switch in promoting lung squamous cell carcinoma from different cells of origin

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Item Type:Article
Title:SOX2 is the determining oncogenic switch in promoting lung squamous cell carcinoma from different cells of origin
Creators Name:Ferone, G. and Song, J.Y. and Sutherland, K.D. and Bhaskaran, R. and Monkhorst, K. and Lambooij, J.P. and Proost, N. and Gargiulo, G. and Berns, A.
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.
Keywords:Animal Disease Models, Cell Proliferation, Fibroblast Growth Factor Receptor Type 1, Genetic Transcription, Lung Neoplasms, Neoplastic Gene Expression Regulation, SOXB1 Transcription Factors, Squamous Cell Carcinoma, Tumor Microenvironment, Animals, Mice
Source:Cancer Cell
ISSN:1535-6108
Publisher:Cell Press / Elsevier (U.S.A.)
Volume:30
Number:4
Page Range:519-532
Date:10 October 2016
Official Publication:https://doi.org/10.1016/j.ccell.2016.09.001
PubMed:View item in PubMed

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