Details

Autor(en) / Beteiligte

• Ferone, Giustina
• Song, Ji-Ying
• Sutherland, Kate D.
• Bhaskaran, Rajith
• Monkhorst, Kim
• Lambooij, Jan-Paul
• Proost, Natalie
• Gargiulo, Gaetano
• Berns, Anton

Titel

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

Ist Teil von

• Cancer cell, 2016-10, Vol.30 (4), p.519-532

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Pten;Cdkn2ab loss causes a diversity of tumors in tracheobronchial basal cells•SOX2 overexpression is crucial in promoting LSCC upon loss of Pten;Cdkn2ab•Sox2;Pten;Cdkn2ab mice develop LSCC from Basal, Alveolar type 2, and Club cells•Mouse LSCC phenotypically and molecularly resembles the human counterpart Ferone et al. establish mouse models bearing various combinations of genetic alterations commonly found in human lung squamous cell carcinoma and show that SOX2, but not FGFR1, overexpression induces the squamous cell fate from different cells of origin carrying the same combined Cdkn2ab and Pten loss.