Expression of Transcription Factor TP63 Reprograms Squamous Pancreatic Ductal Adenocarcinoma Cells

By Riya Gandhi ‘22

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Figure 1. Not only does pancreatic cancer progress quickly, but it is often hard to diagnose.

Although pancreatic cancer is not the most common type of cancer, the prognosis for those diagnosed with the disease is very poor. Much like any other cancer, pancreatic cancer develops when cells in the organ multiply at an uncontrollable rate. Pancreatic ductal adenocarcinoma (PDA), the most common type of pancreatic cancer, garnered the attention of researchers at Cold Spring Harbor Laboratory in Cold Spring Harbor, New York.

Under head researcher Tim Somerville, researchers from this laboratory joined forces with researchers from Stony Brook University to discover that a transcription factor (TF) known as TP63 is responsible for reprogramming squamous enhancers to manage squamous differentiation. These enhancers are genes that cause the adenocarcinomas to express more squamous lineage markers, thereby increasing the aggressiveness of the tumor. To come to this conclusion, the researchers first evaluated pre-existing transcriptome analyses of PDA tumors and deduced that the expression of TP63 is highly enhanced in squamous-subtype tumors. By analyzing transcriptomes, the sum of all the messenger RNA molecules expressed from the genes of an organism, researchers determined the location and timing of this gene. Next, using RT-PCR analysis, they concluded that ΔNp63 is an isoform that is specifically expressed in the samples used and is therefore an oncogenic form of the transcription factor. After that, using RNA-sequencing data and transcriptome analysis, the researchers discovered that expression of this TF installs and sustains the enhancer landscape. Further experimentation revealed that the reprogramming yields aggressive tumor behavior, such as increased invasion and growth. Lastly, the team deduced that squamous PDA cells express TP63.

This experiment is crucial to the pancreatic cancer scene, as it reveals a possible cause of the severity of one of the phenotypes of the disease. Ultimately, the poor prognosis may be explained by the reprogramming uncovered in this study, thereby showing the importance of the role that reprogramming can play in the human body. The researchers hope that future research will uncover methods by which to reverse this or halt the process.

 

References

  1. T Somerville, et. al., TP63-mediated enhancer reprogramming drives the squamous subtype of pancreatic ductal adenocarcinoma. Cell Reports 25, 1741–1755 (2018). doi: https://doi.org/10.1016/j.celrep.2018.10.051.  
  2. Image retrieved from: https://www.pexels.com/photo/1415554/
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