The miR-200 microRNA family suppresses the epithelial–mesenchymal transition (EMT) to promote the reverse process, MET; however, there are conflicting reports on its role in metastasis. Korpal et al. (Nature Med. 17, 1101–1108; 2011) now show that miR-200 microRNAs promote metastatic colonization by regulating the tumour cell secretome.

Analysis of human breast tumour and lung metastasis samples as well as cancer cell lines correlated miR-200 expression with metastatic potential and poor distant relapse-free survival. miR-200 overexpression reduced entry of tumour cells into the circulation of mice, potentially by inhibiting EMT, but increased the lung-colonization ability of poorly metastatic cancer cell lines. This was not phenocopied by overexpresion of E-cadherin, a known MET-mediator upregulated by miR-200. Gene expression and mass-spectrometry analyses identified Sec23a, a secretory pathway component, as a miR-200 target, and Sec23a depletion, similarly to miR-200 overexpression, suppressed metastatic colonization. Mass-spectrometry analysis of conditioned media from Sec23a-depleted tumour cells revealed reduced secretion of a protein set, the low expression of which correlated with low relapse-free survival. Depletion of two such factors, Igfbp4 and Tinagl1, increased metastatic colonization implicating them in metastasis suppression.

These findings indicate that although miR-200 microRNAs may suppress EMT and early tumour cell dissemination, they promote metastatic colonization of cells that successfully enter the circulation by inhibiting secretion of metastasis suppressors.