Extracellular matrix protein 1 recruits moesin to facilitate invadopodia formation and breast cancer metastasis.

Invadopodia are actin-based cortical protrusions of tumour cells, and required for stromal invasion and metastasis. Extracellular matrix protein 1 (ECM1) has long been regarded as a secretory protein, but the mechanism of its precise functions in tumour cells is still obscure. Recently published data suggested a function of ECM1 in remodelling the actin cytoskeleton; however, its role in invadopodia formation remains unknown. Here, we demonstrated for the first time that ECM1 was a membrane protein and was essential for invadopodia formation by breast cancer cells. ECM1 depletion attenuated the ability of tumour cells to matrix attachment, invasion, and spontaneous metastasis to the lungs of mice. Additionally, co-expression of ECM1 and moesin (MSN) was closely related to aggressive breast cancer phenotypes. ECM1 interacted with MSN and recruited it adjacent to the membrane in order to promote MSN membrane translocation and phosphorylation, which facilitated invadopodia formation by breast cancer cells. These results elucidate a novel mechanism underlying the role of ECM1 in breast cancer metastasis and suggest ECM1 as a potential therapeutic target for overcoming tumour dissemination.

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