SOX2 Is the Determining Oncogenic Switch in Promoting Lung Squamous Cell Carcinoma from Different Cells of Origin

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 predominan...

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Bibliographic Details
Published in:Cancer cell Vol. 30; no. 4; pp. 519 - 532
Main Authors: Ferone, Giustina, Song, Ji-Ying, Sutherland, Kate D, Bhaskaran, Rajith, Monkhorst, Kim, Lambooij, Jan-Paul, Proost, Natalie, Gargiulo, Gaetano, Berns, Anton
Format: Journal Article
Language:English
Published: United States 10.10.2016
Subjects:
Animals
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - pathology
Cell Proliferation - genetics
Disease Models, Animal
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Mice
Receptor, Fibroblast Growth Factor, Type 1 - biosynthesis
Receptor, Fibroblast Growth Factor, Type 1 - genetics
SOXB1 Transcription Factors - genetics
Transcription, Genetic
Tumor Microenvironment
ISSN:1878-3686
Online Access:Get more information
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Summary: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.
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ISSN:1878-3686
DOI:10.1016/j.ccell.2016.09.001