In this image of breast tumor cells, amyloid plaques appear as blue dots. Preventing the disaggregation of such plaques, which form as part of a reversible stress response, could keep tumor cells dormant. [Sylvester Comprehensive Cancer Center]
In this image of breast tumor cells, amyloid plaques appear as blue dots. Preventing the disaggregation of such plaques, which form as part of a reversible stress response, could keep tumor cells dormant. [Sylvester Comprehensive Cancer Center]

Amyloid bodies are usually unhealthy developments, most notably in Alzheimer’s disease. Yet amyloid bodies, which are aggregates of alternatively folded proteins, may point to a new form of cancer therapy. Amyloid bodies put cells—including cancer cells—into a dormant state. Unfortunately, in cancer cells, amyloid bodies sometimes disaggregate, and the proteins that are released tend to resume their typical folds. The result: Cancer cells are reactivated. But what if disaggregation of amyloid bodies in cancer cells could be prevented? The cancer cells wouldn’t die. They would, however, stay dormant—and they would stop contributing to the progression of cancer.

New details on the formation of amyloid bodies have been uncovered by researchers at the University of Miami Miller School of Medicine. These researchers, led by Stephen Lee, Ph.D., have learned that the formation of amyloid bodies could be a reversible response to cell stress. These findings, applied to cancer, could lead to novel therapies.

Details of the work appeared October 6 in the journal Developmental Cell, in an article entitled, “Adaptation to Stressors by Systemic Protein Amyloidogenesis.” The article described how the scientists uncover a systemic program that leverages the amyloidogenic propensity of proteins to regulate cell adaptation to stressors.

“A discrete peptidic sequence, termed the amyloid-converting motif (ACM), is capable of targeting proteins to the A-bodies by interacting with ribosomal intergenic noncoding RNA (rIGSRNA),” wrote the article’s authors. “The pathological β-amyloid peptide, involved in Alzheimer's disease, displays ACM-like activity and undergoes stimuli-mediated amyloidogenesis in vivo. Upon signal termination, elements of the heat-shock chaperone pathway disaggregate the A-bodies.”

These mechanistic details are relevant not only to Alzheimer’s, but to cancer, too. The mechanism, the authors suggest, is part of a stress response that enables cells to store large quantities of proteins and enter a dormant state. Amyloidogenesis enables cells to remain viable during prolonged periods of extracellular stress, highlighting the nontoxic and protective nature of the process, not just in cancer cells.

“The amyloid state of protein organization is typically associated with debilitating human neuropathies and rarely observed in physiology,” said Dr. Lee. “Yet, we found that a large number of proteins are stored as amyloid bodies in cancer cells that are dormant. The heat shock chaperone pathway can disaggregate the amyloid bodies and turn the dormant cancer cells into active, progressing cancer cells.”

“If we can stop the amyloid bodies from disaggregating in cancer cells, the hope is that they will remain dormant indefinitely. In addition, we may also be able to turn active cancer cells into dormant ones by encouraging them to store the proteins as amyloid bodies.”

Dr. Lee is optimistic this approach could become a novel way of treating cancer. He points out that there are already drugs on the market, and others are being studied, that target the rIGSRNA as well as the heat shock chaperone pathway.








This site uses Akismet to reduce spam. Learn how your comment data is processed.