The fact that in a previous study with B16-F1 mouse melanoma cells loss of Ena/VASP did not impair invasion in a 3D Matrigel environment (Damiano-Guercio et al., 2020) is most likely indicative of the distinct migration modes employed by confined DCs and mesenchymal cells and confirms the necessity to study the roles and interplay of the diverse actin nucleators in different cell types to unravel the cell-type specific adaptations of the actin nucleation machinery. The gene discussed is ENAH; the disease is melanoma.