The role of SOX2 in small cell lung cancer, lung adenocarcinoma and squamous cell carcinoma of the lung

被引:63
作者
Karachaliou, Niki [1 ]
Rosell, Rafael [1 ,2 ]
Viteri, Santiago [1 ]
机构
[1] Dexeus Univ Inst, Pangaea Biotech, Barcelona, Spain
[2] Hosp Germans Trias i Pujol, Catalan Inst Oncol, Badalona, Spain
关键词
SOX2; transcription factor; non-small cell lung cancer; small-cell lung cancer; cancer stem cells;
D O I
10.3978/j.issn.2218-6751.2013.01.01
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
SOX2 is a stem cell transcription factor that plays a crucial role in the regulation of embryonic development. It is one of the genes in a set of factors (Oct4, SOX2, Nanog) that are able to reprogram human somatic cells to pluripotent stem cells. Overexpression of SOX2 has been described in all types of lung cancer tissues, including small cell and squamous cell carcinoma but also adenocarcinoma. An indepth view of the spectrum of genomic alterations in small cell lung cancer (SCLC) has identified SOX2 as a potential target for therapeutic intervention. Amplification of 3q, the most common genomic aberration in squamous lung cancer, has been demonstrated in the evolution of preinvasive squamous lung cancer and implicates SOX2 as a key target of this dynamic process, making SOX2 and its downstream effector components potential targets for biological therapeutics of squamous carcinomas. SOX2 is expressed in nearly 20% of lung adenocarcinoma and is associated with poor prognosis. SOX2 activity was found to promote squamous identity instead of a loss of cellular differentiation consistent with the role of SOX2 as a "lineage-survival oncogene." Interestingly, SOX2 transcription factor is the predominant downstream target of EGFR signaling and plays a major role in self-renewal growth and expansion of side population cells. In light of the complex actions of SOX2 in regulating normal and tumor development, the elucidation of SOX2-dependent pathways may identify new therapeutic vulnerabilities in lung cancer and uncover additional common pathways between cancer, normal development, and the maintenance of pluripotency.
引用
收藏
页码:172 / 179
页数:8
相关论文
共 43 条
[1]   Expression of Pluripotent Stem Cell Reprogramming Factors by Prostate Tumor Initiating Cells [J].
Bae, Kyung-Mi ;
Su, Zhen ;
Frye, Carole ;
McClellan, Steve ;
Allan, Robert W. ;
Andrejewski, Joseph T. ;
Kelley, Vicky ;
Jorgensen, Marda ;
Steindler, Dennis A. ;
Vieweg, Johannes ;
Siemann, Dietmar W. .
JOURNAL OF UROLOGY, 2010, 183 (05) :2045-2053
[2]   SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas [J].
Bass, Adam J. ;
Watanabe, Hideo ;
Mermel, Craig H. ;
Yu, Soyoung ;
Perner, Sven ;
Verhaak, Roel G. ;
Kim, So Young ;
Wardwell, Leslie ;
Tamayo, Pablo ;
Gat-Viks, Irit ;
Ramos, Alex H. ;
Woo, Michele S. ;
Weir, Barbara A. ;
Getz, Gad ;
Beroukhim, Rameen ;
O'Kelly, Michael ;
Dutt, Amit ;
Rozenblatt-Rosen, Orit ;
Dziunycz, Piotr ;
Komisarof, Justin ;
Chirieac, Lucian R. ;
LaFargue, Christopher J. ;
Scheble, Veit ;
Wilbertz, Theresia ;
Ma, Changqing ;
Rao, Shilpa ;
Nakagawa, Hiroshi ;
Stairs, Douglas B. ;
Lin, Lin ;
Giordano, Thomas J. ;
Wagner, Patrick ;
Minna, John D. ;
Gazdar, Adi F. ;
Zhu, Chang Qi ;
Brose, Marcia S. ;
Cecconello, Ivan ;
Ribeiro, Ulysses, Jr. ;
Marie, Suely K. ;
Dahl, Olav ;
Shivdasani, Ramesh A. ;
Tsao, Ming-Sound ;
Rubin, Mark A. ;
Wong, Kwok K. ;
Regev, Aviv ;
Hahn, William C. ;
Beer, David G. ;
Rustgi, Anil K. ;
Meyerson, Matthew .
NATURE GENETICS, 2009, 41 (11) :1238-U105
[3]   Sox2 maintains self renewal of tumor-initiating cells in osteosarcomas [J].
Basu-Roy, U. ;
Seo, E. ;
Ramanathapuram, L. ;
Rapp, T. B. ;
Perry, J. A. ;
Orkin, S. H. ;
Mansukhani, A. ;
Basilico, C. .
ONCOGENE, 2012, 31 (18) :2270-2282
[4]   Vertebrate neurogenesis is counteracted by Sox1-3 activity [J].
Bylund, M ;
Andersson, E ;
Novitch, BG ;
Muhr, J .
NATURE NEUROSCIENCE, 2003, 6 (11) :1162-1168
[5]   Detection of MET and SOX2 amplification by quantitative real-time PCR in non-small cell lung carcinoma [J].
Cai, Yi-Ran ;
Zhang, Hai-Qing ;
Zhang, Zong-De ;
Mu, Jing ;
Li, Zi-Hui .
ONCOLOGY LETTERS, 2011, 2 (02) :257-264
[6]  
Chen SS, 2012, PLOS ONE, V7, DOI [10.1371/journal.pone.0050456, 10.1371/journal.pone.0036784, 10.1371/journal.pone.0049275, 10.1371/journal.pone.0045763]
[7]   The molecular mechanism governing the oncogenic potential of SOX2 in breast cancer [J].
Chen, Yupeng ;
Shi, Lei ;
Zhang, Lirong ;
Li, Ruifang ;
Liang, Jing ;
Yu, Wenhua ;
Sun, Luyang ;
Yang, Xiaohan ;
Wang, Yan ;
Zhang, Yu ;
Shang, Yongfeng .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (26) :17969-17978
[8]   Recurrent Copy Number Gain of Transcription Factor SOX2 and Corresponding High Protein Expression in Oral Squamous Cell Carcinoma [J].
Freier, Koija ;
Knoepfle, Karl ;
Flechtenmacher, Christa ;
Pungs, Susanne ;
Devens, Frauke ;
Toedt, Grischa ;
Hofele, Christof ;
Joos, Stefan ;
Lichter, Peter ;
Radwirnmer, Bernhard .
GENES CHROMOSOMES & CANCER, 2010, 49 (01) :9-16
[9]   SOX2 Silencing in Glioblastoma Tumor-Initiating Cells Causes Stop of Proliferation and Loss of Tumorigenicity [J].
Gangemi, Rosaria Maria Rita ;
Griffero, Fabrizio ;
Marubbi, Daniela ;
Perera, Marzia ;
Capra, Maria Cristina ;
Malatesta, Paolo ;
Ravetti, Gian Luigi ;
Zona, Gian Luigi ;
Daga, Antonio ;
Corte, Giorgio .
STEM CELLS, 2009, 27 (01) :40-48
[10]   Sox2 is important for two crucial processes in lung development: Branching morphogenesis and epithelial cell differentiation [J].
Gontan, Cristina ;
de Munck, Anne ;
Vermeij, Marcel ;
Grosveld, Frank ;
Tibboel, Dick ;
Rottier, Robbert .
DEVELOPMENTAL BIOLOGY, 2008, 317 (01) :296-309