Researchers have discovered that some proteins that have an influence on the progression and metastasis of cancer are stored away inside of dormant cancer cells, like amyloid bodies that are seen in some neurological disorders. When the amyloid bodies break up, the cell wakes up and is active again. Investigators at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine have published these findings
in Developmental Cell.
Amyloid bodies are groups of proteins that form into aggregates of fine fibers that coalesce as sheets. Amyloids are known to play a part in the development of several neurological diseases like Alzheimer's and Parkinson's disease. Their exact role is still unknown, however. This work may indicate a new avenue for the development of therapeutics for some kinds of cancer.
"The amyloid state of protein organization is typically associated with debilitating human neuropathies and rarely observed in physiology," said the corresponding author of the study, Stephen Lee, the Director of the Tumor Biology Program at Sylvester, and a Professor of Biochemistry and Molecular Biology at the Miller School. "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."
Long intergenic non-coding RNAs (lincRNAs) are a relatively new class of regulatory molecule with poorly understood functions. The researchers determined that lincRNA regulates the formation of amyloids in cancer cells, and as such it’s a prime target for drug development.
"If we can stop the amyloid bodies from disaggregating in cancer cells, the hope is that they will remain dormant indefinitely," explained Lee. "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."
The creation of amyloids allows cells to survive during prolonged periods of extracellular stress, suggesting there is amyloids have a protective function; they may not always be toxic to cells, and that is not restricted to cancer cells.
"Following this approach, we wouldn't necessarily rid the body of cancer cells, but we would keep them inactive - shut off, if you will - and not allow them to become active again," said Lee. "I am optimistic this could become a novel way of treating cancer. There are already drugs on the market, and others are being studied, that target the ribosomal intergenic noncoding RNA as well as the heat shock chaperone pathway."
For more information on long non-coding RNAs, watch the video below from Genetics Professor Ahmad Khalil.
, via University of Miami
, Developmental Cell