It is well-recognized that the majority of cancer-related deaths is attributed to metastasis,
which can arise from virtually any type of tumor. Metastasis is a complex multistep
process wherein cancer cells must break away from the primary tumor, intravasate into the
circulatory or lymphatic systems, extravasate, proliferate and eventually colonize secondary
sites. Since these molecular processes involve the coordinated actions of numerous proteins,
targeted disruptions of key players along these pathways represent possible therapeutic interventions
to impede metastasis formation and reduce cancer mortality. A diverse group of proteins
with demonstrated ability to inhibit metastatic colonization have been identified and they
are collectively known as metastasis suppressors. Given that the metastasis suppressors are
often downregulated in tumors, drug-induced re-expression or upregulation of these proteins
represents a promising approach to limit metastasis. Indeed, over 40 compounds are known to
exhibit efficacy in upregulating the expression of metastasis suppressors via transcriptional or
post-transcriptional mechanisms, and the most promising ones are being evaluated for their
translational potentials. These small molecules range from natural products to drugs in clinical
use and they apparently target different molecular pathways, reflecting the diverse nature of
the metastasis suppressors. In this review, we provide an overview of the different classes of
compounds known to possess the ability to upregulate one or more metastasis suppressors,
with an emphasis on their mechanisms of action and therapeutic potentials.
Catalytic domain of PRL-3 plays an essential role in tumor metastasis: Formation of PRL-3 tumors inside the blood vessels
