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MT1-MMP as a downstream target of BCR-ABL/ABL interactor 1 signaling: polarized distribution and involvement in BCR-ABL-stimulated leukemic cell migration

Leukemia volume 22, pages 1053–1056 (2008)Cite this article

Human chronic myelogenous leukemia (CML) and a subset of acute lymphocytic leukemia (ALL) are caused by expression of Bcr-Abl, a fusion gene generated by reciprocal t(9;22)(q34;q11) chromosome translocation. Bcr-Abl-positive leukemias are characterized by premature release of myeloid and lymphoid lineage cells from bone marrow, followed by expansion of these cells in peripheral blood and infiltration of organs such as spleen, liver and lung. The progression of these diseases involves not only accelerated cell proliferation and enhanced cell survival, but also increased cell motility and active invasion of leukemic cells through blood vessel and matrix barriers. The mechanism by which Bcr-Abl induces increased motility and invasion of leukemic cells is not completely understood.

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a member of transmembrane metalloproteinases, which is responsible for the degradation of a variety of extracellular matrix (ECM).1 MT1-MMP is also an activator of proMMP2 as well as proMMP13 and is a key regulator of cell migration and invasion.1, 2 In migrating cells, MT1-MMP is enriched in migration structures such as lamellipodia, whereas in some tumor cells it is found to localize to a specialized migrating/invasive structure named invadopodium.3 This polarized membrane distribution of MT1-MMP is believed to be critical for cell migration and tumor metastasis. Although available evidence suggests that the interactions of MT1-MMP with transmembrane adhesion molecules and filamentous actin (F-actin) may contribute to its polarized distribution in tumor cells,1 the signaling pathways leading to these interactions remain to be elucidated.

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Acknowledgements

This work was supported by NIH/NCI Grant R01 CA094921 (Z Dai) and NIH/NIDDK Grant K01 DK067191 (Y Tao).

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Authors and Affiliations

  1. State Key Lab for Agro-Biotechnology, College of Biological Sciences, China Agricultural University, Beijing, China

    X Sun & B Wang

  2. Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, TX, USA

    X Sun, W Yu, Y Tao & Z Dai

  3. Department of Medicine, University of Colorado Health Sciences Center, Denver, CO, USA

    Y Li

  4. Stem Cell Transplant Program, Texas Tech University Health Sciences Center, Lubbock, TX, USA

    Z Dai

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  1. X Sun
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Correspondence to Z Dai.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Sun, X., Li, Y., Yu, W. et al. MT1-MMP as a downstream target of BCR-ABL/ABL interactor 1 signaling: polarized distribution and involvement in BCR-ABL-stimulated leukemic cell migration. Leukemia 22, 1053–1056 (2008). https://doi.org/10.1038/sj.leu.2404990

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