Diverse matrix metalloproteinase functions regulate cancer amoeboid migration

Jose L Orgaz, Pahini Pandya, Rimple Dalmeida, Panagiotis Karagiannis, Berta Sanchez-Laorden, Amaya Viros, Jean Albrengues, Frank O Nestle, Anne J Ridley, Cedric Gaggioli, Richard Marais, Sophia N Karagiannis, Victoria Sanz Moreno

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Rounded-amoeboid cancer cells use actomyosin contractility driven by Rho-ROCK and JAK-STAT3 to migrate efficiently. It has been suggested that rounded-amoeboid cancer cells do not require matrix metalloproteinases (MMPs) to invade. Here we compare MMP levels in rounded-amoeboid and elongated-mesenchymal melanoma cells. Surprisingly, we find that rounded-amoeboid melanoma cells secrete higher levels of several MMPs, including collagenase MMP-13 and gelatinase MMP-9. As a result, rounded-amoeboid melanoma cells degrade collagen I more efficiently than elongated-mesenchymal cells. Furthermore, using a non-catalytic mechanism, MMP-9 promotes rounded-amoeboid 3D migration through regulation of actomyosin contractility via CD44 receptor. MMP-9 is upregulated in a panel of rounded-amoeboid compared with elongated-mesenchymal melanoma cell lines and its levels are controlled by ROCK-JAK-STAT3 signalling. MMP-9 expression increases during melanoma progression and it is particularly prominent in the invasive fronts of lesions, correlating with cell roundness. Therefore, rounded-amoeboid cells use both catalytic and non-catalytic activities of MMPs for invasion.
Original languageEnglish
Article number4255
Number of pages13
JournalNature Communications
Early online date25 Jun 2014
Publication statusPublished - 25 Jun 2014


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