Tetraspanins regulate tumour-cell metastasis through effects on signalling pathways and integrin-dependent interactions with the extracellular matrix. On , Christopher Stipp and colleagues investigate how the tetraspanin CD151 regulates interactions between tumour cells, and show that it is important for maintaining the stability of E-cadherin-based cell-cell junctions. By knocking down CD151 expression in epithelial carcinoma cells, they show that CD151 silencing causes an increase in the rate of collective cell migration, despite a decrease in the velocity of single cells. Microscopic analysis reveals that the junctional localisation of E-cadherin is perturbed in CD151-silenced cells, and adhesion assays show that, although E-cadherin-based junctions can initially form in the absence of CD151 expression, they are unstable compared with junctions in wild-type cultures. But CD151 and E-cadherin do not physically interact, so how does CD151 mediate its effect? CD151-silenced cells are shown to have increased activity of the small GTPase RhoA, and to form more dynamic monolayers than wild-type cells. CD151 has been implicated as a promoter of metastasis in some settings, but these results suggest that it also negatively regulates metastasis by suppressing RhoA activity, thereby stabilising junctions between E-cadherin-expressing tumour cells.
