Journal article
SOX2 Is the Determining Oncogenic Switch in Promoting Lung Squamous Cell Carcinoma from Different Cells of Origin
G Ferone, JY Song, KD Sutherland, R Bhaskaran, K Monkhorst, JP Lambooij, N Proost, G Gargiulo, A Berns
Cancer Cell | CELL PRESS | Published : 2016
Open access
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 th..
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Awarded by European Commission
Funding Acknowledgements
We wish to thank members of the animal facility of the Netherlands Cancer Institute for maintaining the mice; the Animal Pathology department for producing high-quality histopathological preparations; the NKI-AVL core facility Molecular Pathology & Biobanking for supplying NKI-AVL Biobank material and laboratory support; Ivo Huijbers and Colin Pritchard for assisting in generating the mutant ESC lines; and Sarah Best for experiments that were not included in the final manuscript. We wish to thank Paul Krimpenfort for his input during this work and critically reading the manuscript. This study was supported by a WKO grant to A.B. by the Dutch Cancer Society and by a Synergy ERC grant (COMBATCANCER) in which A.B. is one of the principal investigators. K.D.S. is a recipient of a National Health and Medical Research Council of Australia Overseas based Biomedical Training Fellowship (No. 516781). This work also was made possible through Victorian State Government Operational Infrastructure Support and Australian Government IRIISS, and Worldwide Cancer Research grant 14-0433.