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.
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.
Our findings highlight a cell-lineage gene expression pattern for the stem cell transcriptional factor SOX2 in the pathogenesis of lung SCCs and suggest a differential activation of stem cell-related pathways between squamous cell carcinomas and adenocarcinomas of the lung.
Here we present these studies and additional data from integrative transcriptomic analyses of primary lung SCC that altogether shed new light and open new exciting perspectives on the multiples roles that SOX2 exerts all along SCC carcinogenesis.
These results indicate that the SOX2 transcription factor, a major regulator of stem cell function, is also an oncogene and a driver gene for the recurrent 3q26.33 amplifications in lung SCC.
We conclude that SOX2 amplification and consequent SOX2 protein overexpression may represent important mechanisms of tumor initiation and progression in a considerable subset of squamous cell carcinomas.
Recently, overexpression and gene amplification of Sox2 have been associated with the development of squamous cell carcinoma in multiple tissues such as the lung and esophagus.
Our results suggest that sex-determining region Y-box 2 amplification is not an early event in squamous carcinogenesis and is important for progression in a subset of squamous cell carcinoma.
These findings indicate that basal stem/progenitor cells are the cells of origin of squamous carcinoma and that cooperation between Sox2 and microenvironment-activated Stat3 is required for Sox2-driven tumorigenesis.
The identification of the SCC-associated interaction between SOX2 and p63 will enable deeper characterization the downstream targets of this interaction in SCC and normal squamous epithelial physiology.
We demonstrate that Sox2 is required for SCC growth in mouse and human, where it enhances Nrp1/Vegf signalling to promote the expansion of TICs along the tumour-stroma interface.
Recurrent gain on chromosome 3q26 encompassing the gene locus for the transcription factor SOX2 is a frequent event in human squamous cell carcinoma, including head and neck squamous cell carcinoma (HNSCC).
The pooling analyses revealed that there were significant associations between SOX2 DNA amplification and clinical features of NSCLC, gender, smoking status, squamous cell cancer (SCC) histology, and differentiations.
Additionally, clinical results further revealed that Sox2 and Oct4 expression was inversely correlated with miR-145 in the tissues of areca quid chewing-associated OSCC patients.