Both the Wnt/β-catenin pathway and the extracellular-signal-regulated kinase (ERK) pathway are implicated in cellular transformation but to date no significant interactions between these pathways have been identified. Now, on , Kang-Yell Choi and colleagues report that Wnt3a (which, like other Wnt proteins, is involved in differentiation, cell migration and cell proliferation) stimulates the growth of mouse fibroblast cells both through activation of the canonical Wnt signalling pathway and through the ERK pathway. The authors show that Wnt3a-induced proliferation of NIH3T3 cells increases both β-catenin levels and the activity of the Raf-1-MEK-ERK cascade. Furthermore, RNAi directed against β-catenin reduces Wnt3a-induced proliferation, as does the MEK inhibitor U0126 or RNAi directed against ERK. However, although basal ERK activities are reduced by RNAi that targets β-catenin, Wnt3a still stimulates cell growth. These and other results lead the authors to propose that Wnt3a stimulates cell proliferation by activating the ERK pathway both directly, in a β-catenin-independent manner, and indirectly, via a β-catenin-dependent route.
