In epithelial cancer metastasis, the tissue-supporting basement membrane or extracellular matrix (ECM) is breached. Actin-rich cellular protrusions – invadopodia – facilitate invasion and degradation of the ECM through secreted matrix metalloproteinase (MMP) enzymes. However, the mechanism and pathways leading to invadopodia extension in cancer metastasis are not well understood. In this issue (p. 4341), Rytis Prekeris and co-workers investigate the pathways of invadopodia formation and ECM degradation during breast cancer cell invasion in vivo. The authors show that the Rab40b GTPase, the levels of which are increased in metastatic breast cancer, is required for tumour growth and invadopodia extension in vivo. Further, they identify scaffolding protein tyrosine kinase substrate 5 (Tks5), a known regulator of invadopodia function, as a Rab40b binding partner. The expression levels of Rab40b and Tks5 are found to be controlled by the tumour suppressor microRNA miR-204. In breast cancer cells, miR-204 downregulates levels of Rab40b and Tks5 to reduce the secretion of MMP2 and MMP9 for ECM degradation. Together, these data highlight a Rab40b- and Tks5-dependent transport pathway involving a microRNA for invadopodia-associated ECM degradation during breast cancer metastasis.