title: Diverse matrix metalloproteinase functions regulate cancer amoeboid migration.
abstract: 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.
authors: Tumour Plasticity Team, Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
authors: Jose L
authors: JL
authors: Orgaz
authors: Tumour Plasticity Team, Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
authors: Pahini
authors: P
authors: Pandya
authors: Tumour Plasticity Team, Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
authors: Rimple
authors: R
authors: Dalmeida
authors: NIHR Biomedical Research Centre at Guy's and St Thomas' Hospitals, Cutaneous Medicine and Immunotherapy Unit, St John's Institute of Dermatology, Division of Genetics and Molecular Medicine at Guy's Hospital, King's College London, London SE1 9RT, UK.
authors: Panagiotis
authors: P
authors: Karagiannis
authors: Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
authors: Berta
authors: B
authors: Sanchez-Laorden
authors: Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
authors: Amaya
authors: A
authors: Viros
authors: INSERM, U1081, CNRS, UMR7284, Institute for Research on Cancer and Aging in Nice (IRCAN), Faculté de Médecine, University of Nice Sophia-Antipolis, 28 Avenue de Valombrose, F-06107 Nice, France.
authors: Jean
authors: J
authors: Albrengues
authors: NIHR Biomedical Research Centre at Guy's and St Thomas' Hospitals, Cutaneous Medicine and Immunotherapy Unit, St John's Institute of Dermatology, Division of Genetics and Molecular Medicine at Guy's Hospital, King's College London, London SE1 9RT, UK.
authors: Frank O
authors: FO
authors: Nestle
authors: Cell Signalling in Invasion and Motility Team, Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
authors: Anne J
authors: AJ
authors: Ridley
authors: INSERM, U1081, CNRS, UMR7284, Institute for Research on Cancer and Aging in Nice (IRCAN), Faculté de Médecine, University of Nice Sophia-Antipolis, 28 Avenue de Valombrose, F-06107 Nice, France.
authors: Cedric
authors: C
authors: Gaggioli
authors: Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
authors: Richard
authors: R
authors: Marais
authors: NIHR Biomedical Research Centre at Guy's and St Thomas' Hospitals, Cutaneous Medicine and Immunotherapy Unit, St John's Institute of Dermatology, Division of Genetics and Molecular Medicine at Guy's Hospital, King's College London, London SE1 9RT, UK.
authors: Sophia N
authors: SN
authors: Karagiannis
authors: Tumour Plasticity Team, Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
authors: Victoria
authors: V
authors: Sanz-Moreno
mesh_terms: D000205:Actomyosin / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D050796:STAT3 Transcription Factor; D000205:Actomyosin; D053612:Janus Kinases; D054460:rho-Associated Kinases; D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9