Squamous cell carcinomas (SCC) are aggressive malignancies that arise from the squamous epithelium of various organs, such as the esophagus, head and neck, lungs, and skin. Previous studies showed that two major transcription factors, TP63 and SOX2, affect genomic activation in SCC. Now, researchers at the Singapore Cancer Institute (CSI Singapore) at the National University of Singapore have gone a step further and identified a protein complex specific for SCC activated by TP63 and SOX2 that triggers a cascade of genes that promotes growth of SCC.
The findings of the study were published in the prestigious scientific journal. Communications of nature in September 2018.
Despite significant advances in cancer research, scientists do not fully understand the development and growth of SCC, and effective targeted treatment for the disease has not been developed. Therefore, CSI Singapore researchers have embarked on the study in collaboration with the Cedars-Sinai Medical Center in Los Angeles, USA. UU., To deepen the understanding of SCC biology.
To further investigate the roles of TP63 and SOX2 in the SCCs, the team carried out the epigenomic profile of 4 different types of SCC. Their badysis revealed that TP63 and SOX2, in a cooperative and lineage-specific manner, regulate the expression of CCAT1, a long non-coding RNA that is badociated with multiple cancers, including SCCs, through the activation of its super-promoters and promoters. CCAT1 forms a protein complex with TP63 and SOX2 that then binds to the EGFR superacelerators to further activate two signaling pathways that ultimately trigger the progression of SCC.
This sequence of molecular interactions driven by TP63 and SOX2 that the team discovered opens a series of ways in which the progression of SCC can be interfered. "By elucidating the roles of TP63 and SOX2, we have not only identified possible cancer targets, but we have also shed light on the related pathways that will work in SCCs, and, together, the new knowledge will help pave the way for them to develop. innovative therapies from SCC, "said Professor H Phillip Koeffler, principal investigator at CSI Singapore and principal investigator of this study.
In the future, the research team will look for more advanced mechanisms of the main transcription factors, TP63 and SOX2, in the development of SCC. Through the use of mathematical models, the research team will badyze the interconnected transcriptional circuit formed by these master transcription factors, as well as their interactions with other super-enhancers. This may provide new clues that may contribute to the development of a novel and effective therapeutic modality for SCC.
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Tags: Cancer, Carcinomas, Cell, Gen, Genomic, Light, Neck, Promoter, Protein, Research, RNA, Skin, Transcript