Metastasis suppressor genes: signal transduction, cross-talk and the potential for modulating the behavior of metastatic cells.

In the past decade, research from various disciplines has stimulated a re-evaluation of our ideas of how cancers metastasize. Two important findings have been fundamental to this re-evaluation: that cancer cells are subject to growth regulation at the secondary site and that a specific class of proteins suppresses the metastatic phenotype. These proteins are encoded by metastasis suppressor genes, which are operationally defined as genes that suppress in vivo metastasis without inhibiting primary tumor growth when transfected into metastatic cell lines and injected into experimental animals. Recent biochemical studies have shown that certain metastasis suppressor proteins participate in highly conserved signal transduction cascades that mediate cellular responses to growth factors, cytokines and cellular stresses. Further elucidation of the biochemical foundations of these pathways coupled with strong in vivo studies should give us insight into the mechanisms of cancer metastasis, and may hold important implications for the future of cancer staging and therapy, using both existing and novel modalities.