Mayo Clinic researchers are the first to identify an interaction between two cellular proteins - Skp2 and FOXO1 - that is important for the growth and survival of cancer cells. Researchers also show that this interaction can be chemically reversed to stop cancer tumor growth - a strategy that may lead to new and better cancer treatments.

Their report appears as an electronic advance article of the Proceedings of the National Academy of Sciences. The research was performed on human cells in the laboratory and was found effective against human cancer cells. Researchers say it will be at least a year before the discovery can be applied in a human clinical trial.

For the first time, the Mayo Clinic research group provides laboratory evidence to describe a new mechanism by which cells lose the protection of tumor suppressors - and therefore become vulnerable to cancerous cell growth. In particular, they show that Skp2 is the cellular player that interacts with FOXO1 by tagging it for destruction. This degradation of FOXO1 by high levels of Skp2, in turn, abolishes the ability of FOXO1 to suppress tumors. The result of their experiment indicates that human prostate cancer grows without the protection of the tumor suppressor protein FOXO1. Importantly, they also show that this loss of function can be reversed - even in the presence of high levels of Skp2, by using chemicals that inhibit protein destruction, and thus block Skp2's action against FOXO1.

"The major finding of our studies is that the tumor suppression function of FOXO1 is abolished due to Skp2-mediated protein degradation," says Haojie Huang, Ph.D., the urology researcher who performed the study. Co-investigator Donald J. Tindall, Ph.D., adds, "We've discovered a viable therapeutic target in human cancers, especially those with high levels of Skp2."

The Mayo Clinic researchers' findings suggest a promising new treatment target at which drug designers can aim new therapies for a number of human cancers in which elevated levels of Skp2 have already been documented. These include cancers of the prostate, breast, lymphatic leukemia, small cell lung cancer and certain cancers of the mouth and colorectal cancer.

SOURCES:
Proceedings of the National Academy of Sciences (http://www.pnas.org)
Mayo Clinic (http://www.mayo.edu)