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Master Transcription Factors in Progression of Squamous Cell Carcinoma

By: Melissa E. Fryman, MS
Posted: Wednesday, November 14, 2018

According to a study published in Nature Communications, the progression of squamous cell carcinoma seems to be mediated in part by a newly identified DNA/RNA/protein complex. H. Phillip Koeffler, MD, of Cedars-Sinai Medical Center in Los Angeles, and colleagues at the National University of Singapore, found that the master transcription factors TP63 and SOX2, previously implicated in squamous cell carcinoma, form a complex with the long noncoding RNA CCAT1. The complex, when bound to the super-enhancer region of EGFR, can activate signaling cascades that lead to disease progression.

This study focused on the epigenomic profiles of cell lines from four different esophageal squamous cell carcinomas. Using immunoprecipitation assays, the researchers verified that TP63 and SOX2 physically interact and confirmed, using chromatin immunoprecipitation, that TP63 and SOX2 co-occupy the super-enhancer regions of several oncogenes, including CCAT1. Using a series of gene-silencing and overexpression experiments, the authors found that CCAT1 is a key downstream target of TP63/SOX2, that the cell viability and proliferation of squamous cell carcinoma are dependent on CCAT1, and that CCAT1 activates both MEK/ERK1/2 as well as the PI3K/AKT signaling pathways.

“By elucidating the roles of TP63 and SOX2, we not only have identified possible cancer targets but also shed light on the related pathways [that] will act on [squamous cell carcinomas]. Collectively, the new knowledge will help pave the way for innovative [squamous cell carcinoma] therapies to be developed,” said Professor Koeffler, in a press release from the National University of Singapore.



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