Cancer metastasis: negative regulation by an invasion-suppressor complex

Invasion is the hallmark of tumor malignancy. We situate invasion within microecosystems comprising neoplastic cells as well as host cells. Modulation of invasion within such systems is ascribed to balances between promoter and suppressor pathways. The E-cadherin/alpha-, beta-, gamma-catenin complex has an invasion-suppressor function as evidenced by transfections either with sense cDNA encoding these molecules or with antisense cDNA inhibiting their expression. Loss of heterozygosity at the E-Cadherin (uvo) locus has been reported, but mutations in the E-cadherin gene seem to be rare. Downregulation of E-cadherin occurred at the level of transcription or of mRNA stability. Ex vivo cultures from invasive tumors or metastases produced cells that were homogeneously E-cadherin-positive and noninvasive in vitro. These observations have led to the idea that factors in the host downmodulate the E-cadherin complex and promote invasion most probably in a transient way.