LIM kinase1 modulates function of membrane type matrix metalloproteinase 1: implication in invasion of prostate cancer cells

    Authors

    T. Tapia; R. Ottman;R. Chakrabarti

    Comments

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    Abbreviated Journal Title

    Mol. Cancer

    Keywords

    TRANSCRIPTION FACTOR; ACTIN CYTOSKELETON; TUMOR-METASTASIS; IV; COLLAGENASE; IN-VITRO; ACTIVATION; MT1-MMP; EXPRESSION; DYNAMICS; COFILIN; Biochemistry & Molecular Biology; Oncology

    Abstract

    Background: LIM kinase 1 (LIMK1) is an actin and microtubule cytoskeleton modulatory protein that is overexpressed in a number of cancerous tissues and cells and also promotes invasion and metastasis of prostate and breast cancer cells. Membrane type matrix metalloproteinase 1 (MT1-MMP) is a critical modulator of extracellular matrix (ECM) turnover through pericellular proteolysis and thus plays crucial roles in neoplastic cell invasion and metastasis. MT1-MMP and its substrates pro-MMP-2 and pro-MMP-9 are often overexpressed in a variety of cancers including prostate cancer and the expression levels correlate with the grade of malignancy in prostate cancer cells. The purpose of this study is to determine any functional relation between LIMK1 and MT1-MMP and its implication in cell invasion. Results: Our results showed that treatment with the hydroxamate inhibitor of MT1-MMP, MMP-2 and MMP-9 ilomastat inhibited LIMK1 induced invasion of benign prostate epithelial cells. Over expression of LIMK1 resulted in increased collagenolytic activity of MMP-2, and secretion of pro-MMP2 and pro-MMP-9. Cells over expressing LIMK1 also exhibited increased expression of MT1-MMP, transcriptional activation and its localization to the plasma membrane. LIMK1 physically associates with MT1-MMP and is colocalized with it to the Golgi vesicles. We also noted increased expression of both MT1-MMP and LIMK1 in prostate tumor tissues. Conclusion: Our results provide new information on regulation of MT1-MMP function by LIMK1 and showed for the first time, involvement of MMPs in LIMK1 induced cell invasion.

    Journal Title

    Molecular Cancer

    Volume

    10

    Publication Date

    1-1-2011

    Document Type

    Article

    Language

    English

    First Page

    15

    WOS Identifier

    WOS:000286530200002

    ISSN

    1476-4598

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