A novel method using spider silk may be able to grant a cancer-fighting protein the longevity it needs to protect our cells from cancer, according to new research by the Karolinska Institutet in Sweden. Their study, which was published in the journal Structure, suggests that the addition of spider silk protein to p53, an integral protein that has long been considered a target for cancer treatments, could prevent it from breaking down so rapidly in the cell and potentially increase its proficiency at killing cancer cells.
The team thinks that if this is improved further, spider silk protein may be a possible candidate for an mRNA vaccine in the future.
“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 at Karolinska Institutet, in a statement.
“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.”
P53 is a well-characterized tumor-suppressor protein that has critical roles in preventing cell division from becoming uncontrollable. It acts like a quality-control officer in a sense, binding to DNA and checking it in the event of damage by UV light, chemicals or other genotoxic substances. P53 identifies any faults and "decides" whether they can be fixed, either activating one gene pathway to repair the damage or activating the apoptosis pathway to destroy the cell if the damage is too much. If p53 becomes damaged or faulty, cells can quickly spiral out of control and begin dividing rapidly, creating a tumor. Mutations in p53 are found in around half of all cancers and it is the most common genetic fault in cancer that we are currently aware of.
So, why not just supplement p53 in cells, or increase the activity of the gene that makes p53? Unfortunately, a protein with such complex function is a large and unstable structure, meaning it doesn't stick around in the cell for very long. It would therefore be ideal if scientists could stabilize this protein using another protein, perhaps known for its structural integrity, and the team believed spider silk could be the key.
“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, researcher at the Department of Microbiology, Tumor and Cell Biology.
“We’ve been inspired by how nature creates stable proteins and have used spider silk protein to stabilise p53. Spider silk consists of long chains of highly stable proteins, and is one of nature’s strongest polymers.”
In this pursuit, the researchers fused p53 to an extremely stable and compact spider silk domain. They discovered this new fusion protein was more stable that p53, and "unblocked" p53 translation, creating a biologically-active protein, which could result in it preventing tumors more effectively than standard p53.
The researchers did not test whether their fusion protein actually had an effect on tumor suppression, only identifying that it was stable and biologically active. Future results will illuminate how the fusion protein will interact with other proteins to prevent cancer, as well as whether the spider silk will cause problems in high quantities.