Tetraspanin-enriched microdomain variation as a component of HCC progression. The signaling pathway varies between cell types when differential TEM profiling is expressed following exposure to a cell agonist or through changes in the microenvironment. These variations in signaling can profoundly affect the tumorigenicity and metastatic properties of HCC cells. a) Following stimulation, CD81-associated proteins inhibit tumor cell migration, possibly through a blockade of ezrin-radixin-moesin (ERM) protein activation, inhibiting actin reorganization. b) Reduced expression of CD81 and up-regulation of CD151, α6β1 integrin and ADAM10 foster invasion and possibly metastases through events of actin cortex - membrane destabilization during cell motility.