SOX2 Is an Amplified Lineage Survival Oncogene in Lung and Esophageal Squamous Cell Carcinomas

By A. Bass, H. Watanabe, Craig H. Mermel, Soyoung Yu, S. Perner, R. Verhaak, S. Kim, Leslie H. Wardwell, Pablo Tamayo, Irit Gat-Viks and 38 more. Nature Genetics, 2009

956 citations recorded by the source corpus.

Lineage-survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development. Here we show that a peak of genomic amplification on chromosome 3q26.33 found in squamous cell carcinomas (SCCs) of the lung and esophagus contains the transcription factor gene SOX2, which is mutated in hereditary human esophageal malformations, is necessary for normal esophageal squamous development, promotes differentiation and proliferation of basal tracheal cells and cooperates in induction of pluripotent stem cells. SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 here cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These characteristics identify SOX2 as a lineage-survival oncogene in lung and esophageal SCC.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0d179b60e0a249055a37683f960b3bb190702ac0

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Citations in the corpus

Senescence impairs successful reprogramming to pluripotent stem cells. (2009, background): “SOX2 has been implicated in breast (Chen et al., 2008), esophageal (Bass et al., 2009) and lung cancer (Hussenet and du Manoir, 2010).”
Lessons from the cancer genome. (2013, neutral): “1 in lung adenocarcinoma, SOX2 in esophageal cancer, and CDX2 in colorectal cancer (Bass et al., 2009; Salari et al., 2012; Weir et al., 2007).”
A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets (2012, background): “1 in lung cancer(55) 56 and SOX2 in oesophageal and lung cancers.(57) Indeed, GATA6 has recently been proposed to function as an amplified lineage-survival oncogene in pancreatic cancer,(35) 58 and KLF5 has been shown to be expressed during early development in the cardiovascular system and gastroin”
Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. (2010, background): “Recently, the elegant study by Bass and colleagues (36) demonstrated that the DNA copy numbers of Sox2 were highly”
GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers (2011, methodology): “GISTIC has been applied to multiple cancer types, including glioblastoma [10,15], lung adenocarcinoma [16], melanoma [17], colorectal carcinoma [18], hepatocellular carcinoma [19], ovarian carcinoma [20], medulloblastoma [21], and lung and esophageal squamous carcinoma [22], and has helped identify ”
EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer (2010, background): “In addition, the SOX2 transcription factor, which is required for efficient induced pluripotent stem cell reprogramming is amplified in lung and esophageal squamous cancers, underscoring a role for stem cell factors as oncogenes (Bass et al., 2009; McCaughan et al., 2010; Yuan et al., 2010).”
Sox2+ adult stem/progenitor cells are important for tissue regeneration and survival of mice (2011, positive): “Given the recent recognition that Sox2 can act as an oncogene in squamous cell carcinoma of the lung and esophagus (Bass et al., 2009), it should be interesting to investigate further whether the Sox2-expressing cells, identified here, can act as tumor-initiating cells, and whether Sox2 expression…”