Tetraspanins regulate tumour-cell metastasis through effects on signalling pathways and integrin-dependent interactions with the extracellular matrix. On page 2263, 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.