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

被引：179

作者：

Ferone, Giustina ^{[1
]}

Song, Ji-Ying ^{[2
]}

Sutherland, Kate D. ^{[4
,5
]}

Bhaskaran, Rajith ^{[1
,6
]}

Monkhorst, Kim ^{[3
]}

Lambooij, Jan-Paul ^{[1
]}

Proost, Natalie ^{[1
]}

Gargiulo, Gaetano ^{[7
]}

Berns, Anton ^{[1
,6
]}

机构：

[1] Netherlands Canc Inst, Div Mol Genet, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands

[2] Netherlands Canc Inst, Div Expt Anim Pathol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands

[3] Netherlands Canc Inst, Div Pathol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands

[4] Walter & Eliza Hall Inst Med Res, ACRF Stem Cells & Canc Div, Parkville, Vic 3052, Australia

[5] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia

[6] Skolkovo Innovat Ctr, Skolkovo Inst Sci & Technol, Bldg 5, Moscow 143026, Russia

[7] Max Delbruck Ctr Mol Med, Dept Mol Oncol, Robert Rossle Str 10, D-13092 Berlin, Germany

来源：

CANCER CELL | 2016年 / 30卷 / 04期

基金：

英国医学研究理事会;

关键词：

SUPPRESSOR-CELLS; STEM-CELLS; TUMOR INITIATION; GENE-EXPRESSION; NONSMALL CELL; BASAL-CELLS; MOUSE MODEL; CANCER; P63; PROGENITOR;

D O I：

10.1016/j.ccell.2016.09.001

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：519 / 532

页数：14

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