Diverse matrix metalloproteinase functions regulate cancer amoeboid migration

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-mesench...

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Bibliographic Details
Published in:	Nature communications 2014-06, Vol.5 (1), p.4255-4255, Article 4255
Main Authors:	Orgaz, Jose L, Pandya, Pahini, Dalmeida, Rimple, Karagiannis, Panagiotis, Sanchez-Laorden, Berta, Viros, Amaya, Albrengues, Jean, Nestle, Frank O, Ridley, Anne J, Gaggioli, Cedric, Marais, Richard, Karagiannis, Sophia N, Sanz-Moreno, Victoria
Format:	Article
Language:	eng
Subjects:	Actomyosin - metabolism Cell Line, Tumor Cell Movement Humans Janus Kinases - metabolism Matrix Metalloproteinase 13 - metabolism Matrix Metalloproteinase 9 - metabolism Melanoma - metabolism Melanoma - pathology Neoplasm Invasiveness rho-Associated Kinases - metabolism Signal Transduction STAT3 Transcription Factor - metabolism
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Summary:	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.
ISSN:	2041-1723 2041-1723