More than 90% cancer motility is caused by metastasis that is due to various types of primary cancer cells interact with their microenvironment and accumulate genetic alterations that allow cancer cells to transcend their programmed behavior. Cancer cells thus migrate, and flourish in new tissue habitats, ultimately, cause various organ dysfunctions and death.
Most cancer cases (>95%) are derived from epithelial cells. Several genes have been identified to be associated with epithelial derived cancer metastasis including E-cadherin and dystroglycan. Loss of E-cadherin function is necessary, for epithelial to mesenchymal transition and enabling detachment and reorganization of epithelial-cell sheets during cancer invasion and metastasis. Similarly, loss of functional dystroglycan, a receptor for a number of extracellular matrix proteins, which is essential for all tissues maintain their architecture and morphology, is associated with 70% metastasis. Both proteins are glycosylated proteins. The glycans on the proteins are essential for their functions. Enhance the glycosylation of these proteins can inhibit cancer growth and metastasis. Our drug leads specifically enhance the glycosylation of the proteins, thus they are potential to be used to treat metastasis cancers.