Scientists at the Massachusetts Institute of Technology (MIT) have discovered a “safety net” that allows cancer cells not only to survive potent drugs but also to develop aggressive mutations in environments where healthy cells would perish.
The study, conducted by Matthew D. Shoulders’ laboratory and published in the journal Molecular Cell, focuses on the human body’s most well-known anti-tumor gene, TP53 (also known as p53).
The p53 protein is famously called the “guardian of the genome” because its role is to stop damaged cells from dividing. However, in cancer, this gene is the one that most frequently undergoes mutation. Researchers found that tumor cells create a specialized environment that makes these dangerous changes “viable.“
For proteins to perform their functions, they must “fold” into complex 3D shapes. Mutations often disrupt this folding, which usually leads the cell to destroy the damaged protein. Cancer cells, however, utilize helper proteins called “chaperones” to deliberately maintain these damaged proteins in their correct form. This protective network is managed by a regulator called HSF1, which is permanently “switched on” in tumors, whereas in healthy cells, it is only activated during extreme stress.
Research Findings
As part of the experiment, scientists engineered a specialized line of cancer cells where they could artificially control the activity of the HSF1 regulator chemically, “turning it up” as needed.
The results showed that when HSF1 activity is enhanced, cancer cells much more easily withstand “bad” mutations that would otherwise be lethal to the cell. Specifically, mutations that would normally destabilize and disable the p53 protein’s structure remain stable thanks to the “supportive environment” created by HSF1. Ultimately, this mechanism allows the tumor to retain damaged, aggressive proteins and use them to continue growing and developing without hindrance.
Why Is This Study Important?
This discovery explains why cancer is so resistant to treatment. Until now, attempts to treat cancer by blocking chaperones have been quite difficult; however, this new knowledge will allow doctors to break the cancer’s “safety net” in the future.
If scientists can successfully disable this protective mechanism, the tumor’s own mutations will become the cause of its destruction.
