Cancer cells are full of defective genetic mutations that do not respond to signals that stop them from reproducing. These mutations cause the cancer cells to create a number of dysfunctional proteins, that must be regularly cleaned by the cells. Like regular cells, the cancer cells will die if the garbage protein molecules are not disposed off. Caltech researchers have developed a new treatment that inhibits the ability of cancer cells to clean themselves, filling them up with junk proteins that cause the cells to self-destruct.
Jing Li, a postdoctoral scholar in biology and biological engineering says, “All current cancer drugs that target the proteasome work by inhibiting the protein-chopping enzymes on the inside of the proteasome; therefore they all have similar drawbacks and tend to lose efficacy over time. Our research offers an alternative path to disabling proteasome function, including in cells that no longer respond to the existing drugs.”
The structure within a cell responsible for garbage disposal is known as a proteasome. It is a hollow cylinder that takes in defective cells, chops them up, and then ejects the waste matter. The defective proteins are attached or tagged with smaller proteins that signal the defectiveness of the cell to the proteasome. These tags are removed when the damaged proteins enter the proteasome, or the garbage would be too big to be handled by the disposal. The treatment makes it impossible for the proteasome to fully destroy bad proteins, by inhibiting the part of the proteasome that removes the tags, known as Rpn11.
The cancerous cells quickly start filling with junk, and the resulting stresses are fatal to the cell. The treatment affects the garbage disposal process of even regular cells, but normal cells produce a lot less garbage than cancerous cells. Even a small dose of the treatment can be catastrophic for cancer cells. The research has been published in the scientific journal Nature Chemical Biology.
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