Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
Copper storage diseases: Menkes, Wilson's, and cancer
The trace element copper is vital to the healthy functioning of organisms. Copper is used in a multitude of cellular activities including respiration, angiogenesis, and immune responses. Like other metals, copper homeostasis is a tightly regulated process. Copper is transported from dietary intake through the serum and into cells via a variety of transporters. There are a variety of copper chaperones designed to insure that copper is sequestered from interaction with cellular membranes, proteins, or DNA where its properties can result in oxidative damage. However, there are disease states in which copper transporters crucial to homeostasis are impaired resulting in potentially toxic copper accumulation. Wilson's and Menkes diseases are two such cases. Wilson's disease (hepatolenticular degeneration) is an autosomal recessive disorder resulting in extreme accumulation of copper in the liver with deposits elsewhere in the body. Menkes is characterized by a systemic copper deficiency (different from the liver specificity of Wilson's disease) and is the result of an X-linked recessive mutation in a copper transporter. Uptake of copper is impaired due to inability to remove existing copper from cells primarily in the small intestine. Though the causes are dramatically different, cancer also shares a similar diagnostic in the accumulation of copper in effected tissues. Studies have shown greatly elevated levels of copper in cancer tissues, and some diagnostics and treatments from Wilson's and Menkes diseases, such as copper chelation therapy, have been used in the treatment of cancer. Given the commonality of copper accumulation in these diseases and that common therapies exist between them, it may prove beneficial to study all three diseases in light of copper homeostasis. This review will examine the chemical nature and biological roles of copper, Wilson's and Menkes disease and their therapies, and the use of copper related therapies in cancer.