Spider Silk May Help Treat Cancer
Researchers at Karolinska Institute have found a way of stabilizing the p53 protein, and making it more potent. P53 protects our cells from cancer. By adding a spider silk protein to p53, the researchers have shown that it is possible to create a protein that is more stable and more capable of killing cancer cells.
P53 plays a key role in the body's defense against cancer. If a cell is lacking functional p53, it quickly becomes a cancer cell. And it starts to divide uncontrollably.
"The problem is that cells only make small amounts of p53 and then quickly break it down as it is a very large and disordered protein," says researcher Michael Landreh in a press release issued by Karolinska Institute.
"We've been inspired by how nature creates stable proteins and have used spider silk protein to stabilize p53. Spider silk consists of long chains of highly stable proteins, and is one of nature's strongest polymers."
Discovered in the late 1970s, p53 has been called the guardian of the genome. It can stop cells with DNA damage from turning into cancer cells.
Essentially, p53 shuts down a cell if it detects any damage that could cause the cell to grow into cancer. Mutations of the p53 gene are found in roughly half of all tumors. That makes it the most common genetic change in cancer.
A paper is published in Structure. The researchers report that they attached a small section of a synthetic spider silk protein onto the human p53 protein. When they then introduced it into cells, they found that the cells started to produce p53 in large quantities.
The new protein also proved to be more stable than ordinary p53 and more capable of killing cancer cells. Using electron microscopy, computer simulations, and mass spectrometry, the researchers were able to show that the likely reason for this was the way the spider silk part managed to give structure to p53's disordered sections.
"Creating a more stable variant of p53 in cells is a promising approach to cancer therapy, and now we have a tool for this that's worth exploring," says senior researcher Sir David Lane, who was one of the discoverers of p53.
"We eventually hope to develop an mRNA-based cancer vaccine, but before we do so we need to know how the protein is handled in the cells and if large amounts of it can be toxic."
Writing in The Conversation, Landreh explains that spidroins are a bit like p53. They are proteins that spiders spin into silk. They are also large, floppy, and easily clumped together.
But unlike p53, spidroins are capped by a small part that is very stable. And it can easily be made by the cellular protein production machinery.
“To test if the spider silk-p53 protein is active, we put it into cancer cells that contain so-called ‘reporter genes’, which cause the cell to light up if p53 turns on genes that make the cell stop growing,” says Landreh.
“To our surprise, the fusion protein gave a stronger response than normal p53, which means that we could in principle use the spider silk domain to increase the ability of p53 to shut down cancer cells.”
Landreh comments that, while this research result is not a new cancer therapy, it opens up new possibilities for cancer therapy. The researchers now plan to test how well healthy human cells tolerate the spider silk proteins. They also plan to test whether the addition of spidroins extends the lifetime of the p53 protein inside the cells.
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