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.
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.
In addition, upregulated SOX2 was associated with advanced and metastatic tumors in OSCC patients and was responsible for the drug-resistance property of OSCC cells.
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.
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.
This may be because pathways enriched in the TrkB high expressers, like those involving oncogenes NFE2L2, PIK3CA, and SOX2, are known to have SCC anatomic site-specific effects on progression.
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.
Combining gene targeting with chromatin immunoprecipitation sequencing (ChIP-seq) and transcriptomic analyses reveals that PITX1 cooperates with SOX2 and TRP63 to sustain an SCC-specific transcriptional feed-forward circuit that maintains TPC-renewal, while inhibiting KLF4 expression and preventing KLF4-dependent differentiation.
In the current study we investigated podoplanin (PP) and SOX2 expression in normal squamous epithelium, in CIN 3 and in 16 CIN 3-like SCCs 11 of which also showed a conventional invasive component.
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.
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).
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.
We propose that Oct3/4, Sox2 and Nanog are associated with tumor hypoxia characterized in oral SCC and that these factors may also contribute to the undifferentiated potency observed in oral SCC clinically.
Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter.