Spider silk can fortify the potency of cancer-fighting protein
Strong and flexible, spider silk is one of the most astounding materials in the natural world.
Because of its extraordinary characteristics, it has found its way into medical research ranging from gene therapy to reconstructive surgery.
Now, a team of scientists from the Karolinska Institutet (KI) in Sweden has discovered another use for the material: stabilizing and enhancing p53, a cancer-killing protein.
The p53 protein protects our cells against cancer; however, it breaks down quickly in the cell. By adding spider silk protein to p53, the researchers were able to make it more stable and more potent, effectively demonstrating that it is feasible to develop a protein that is more stable and capable of destroying cancer cells.
p53 protein: "The guardian of the genome"
The KI cancer researchers were investigating how p53, as well as the p53 gene that encodes it, affects cancer development. This protein essentially monitors cell division and stops it if it detects DNA damage or a mutation. This keeps damaged cells from turning cancerous.
It plays such a key role that mutations or other types of dysfunction in the p53 gene have been linked to half of all cancers. This makes it one of the most prevalent genetic changes seen in cancer and a crucial point of focus for researchers looking for novel treatments.
However, the p53 protein has a few shortcomings.
"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," said study author Michael Landreh, in a press release.
Cancer research meets spider silk
To find the solution to this problem, the researchers collaborated with experts from the KI's Department of Biosciences and Nutrition and investigated whether nature could provide some insights, as they were inspired by the way nature makes stable proteins.
After research, the researchers opted to use spider silk protein to stabilize p53 since spider silk is made up of long chains of highly stable proteins, as well as being one of nature's strongest polymers.
A small section of a synthetic spider silk protein was connected to a human p53, resulting in a spider-silk-p53 fusion protein, per the study published in the journal Structure. When the researchers introduced this chimeric protein to cells in vitro, they saw that those cells began to generate it in high quantities, with the protein proving more stable than conventional p53 and with greater cancer-killing properties.
The researchers were able to figure out why adding the spider silk protein had these results. They believe it restores structure to the p53 protein's disordered portions, but the novel protein's structure and effects on healthy cells will need to be studied further.
“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,” said co-author and senior professor Sir David Lane. "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."