Spider silk protein may improve cancer resistance

Swedish scientists have found a way to use spider silk protein to boost p53, a cancer-killing protein in humans.

Flexible yet strong, spider silk is one of the most incredible materials in the natural world. With its superior properties, it has been used in many medical studies, from gene therapy to reconstructive surgery.

In a new study published in the journal Structure on March 14, scientists from the Karolinska Institutet (KI) in Sweden have discovered another unexpected use of this material, which is to help stabilize and increase boosts an anti-cancer protein called p53.

Spider web of the species Argiope amoena.

The p53 protein plays an important role in protecting cells from cancer, in part by detecting and blocking disease-causing gene mutations. If a cell lacks functional p53, it quickly becomes a cancer cell that divides uncontrollably. Therefore, researchers around the world are trying to develop treatments that are somehow based on p53.

"The problem, however, is that cells make only a small amount of p53 and then rapidly break it down because it's a very large and disordered protein," said study lead author Michael Landreh. "We took inspiration from nature, using spider silk proteins to stabilize p53. Spider silk is composed of long chains of highly stable proteins and is one of the strongest natural polymers."

By attaching a small portion of the synthetic spider silk protein to the human p53 protein, and then introducing it into cells, Landreh found, the cells began to produce p53 in large amounts. The new protein was also shown to be more stable than regular p53 and capable of killing cancer cells. Using electron microscopy, computer simulations and mass spectrometry, the team was able to show that the reason for this lies in how the spider silk protein manages to give structure to the disordered portions of p53. .

In the next phase, Landreh and his colleagues plan to study in detail the structure of the protein and how its different parts interact to prevent cancer. They also wanted to understand how cells were affected by the new potent p53 protein.

"Creating a more stable variant of p53 in cells is a promising approach to cancer therapy, and we now have a tool worth exploring," said Senior Professor Sir David Lane at KI, co-author of the study, stressed. "Ultimately, we hope to develop an mRNA-based cancer vaccine, but before we can do that, we need to know how to process the protein in the cell if large amounts of it can be toxic." .

The Karolinska Institute study was supported by the Swedish Strategic Research Fund (SSF), the Swedish Cancer Society, the Swedish Research Council, Vinnova, the Olle Engkvist Foundation, the Swedish Medical Research Association (SSMF), ), Formas and the Åke Wiberg Foundation.