Expression of a specific protein detrimental to early death in pancreatic cancer

Expression of a specific protein detrimental to early death in pancreatic cancer

Cancer cells are often described as cells "gone bad" or "renegade." New research reveals that in some of the deadliest cases of pancreatic cancer, these rebellious cells have an unexpected addiction. Now, scientists are investigating if that addiction can be used to bring about a tumor's end.

The senior author explained that the average pancreatic cancer patient will survive for about two years after diagnosis. However, a notable subgroup succumbs to the disease much earlier--before the end of its first year. The team suspects that a unique protein in the pancreas of these unfortunate patients is a cause.

"We were able to identify a gene [and the protein it produces] called Tumor-Protein 63 (TP63) that is specifically expressed in this aggressive form of pancreatic cancer," said the author.

Protein 63 (P63) is not normally present within pancreas cells. It is necessary for the creation of specialized cells called squamous cells. These are long, thin cells that are required for the formation of skin. When the researchers noticed P63 at work within the pancreas--nowhere near the skin--they knew something was suspicious. P63 was encouraging pancreas cells to grow into things they had no business being!

Further testing revealed that having this squamous-cell-promoting gene inappropriately active within the tumor was making it very easy for new renegade cells to arise and spread to other parts of the body. However, when something is easy, there's usually a catch--even for cancer.

Authors demonstrate that TP63-driven enhancer reprogramming promotes aggressive tumor phenotypes, including enhanced cell motility and invasion, and an accelerated growth of primary PDA tumors and metastases in vivo. This process ultimately leads to a powerful addiction of squamous PDA cells to continuous TP63 expression.

"One of the encouraging findings is that when this happens ... the cancer cells become so reliant on P63 that they actually require P63 for their continued growth," the author explained. "So moving forward, we're looking into approaches to suppress inappropriate P63 activity as a treatment option for patients."

Another goal of the team is to discover why the TP63 gene gets active in the pancreas of specific patients in the first place. "If we can stop it from ever happening," said the author, "it could be really good for the survival of this most vulnerable group of cancer patients."