The occurrence of invasion and metastasis is the major cause for most cancer-related deaths. During metastaticprogression of carcinoma, polarized epithelial tumor cells gain invasive and migratory characteristics, leave theprimary site, invade the basement membrane beneath, intravasate into blood or lymph vessels, transport throughthe circulation, extravasate from the circulation, disseminate into the secondary site, and grow at the metastaticfoci.
Epithelial carcinoma cells disseminate from primary tumor sites by using either collective cell migration(2) or single cell migration such as round shape, non-proteolytic amoeboid migration (3) and mesenchymal-typemovement (4). This phenotypic conversion enables tumor cells dissociate from their original tissue and formmetastasis in distant organ. This epithelial cell plasticity caused by breakdown of epithelial cell homeostasisleading to malignant cancer progression has been associated with the loss of epithelial traits and the acquisitionof migratory phenotype. In carcinomas,cells awakening the event of mesenchymal transition become motile andincrease invasive ability (4). Hence, the phenotypic transition from epithelial to mesenchymal-like cell staterepresents one important mechanism for epithelial plasticity and cancer metastasis.Recent studies have implicated the role of Twist, the basic helix–loop–helix transcription factor in the earlysteps of metastasis (5,6).
Twist has been previously known to be involved in neural crest cell migration andmesoderm differentiationand has recently been identified for genes associated with metastasis to the lungs ofmurine mammary tumor lines. Moreover, studies demonstrate that Twist overexpression results in EMT ofhuman immortalized mammary epithelial cells, which is characterized by downregulation of E-cadherin, betaanditalic gamma-catenin, upregulation of fibronectin and vimentin, spindle-like morphological changes andincreased migratio