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|a Oudin, Madeleine Julie
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|a Massachusetts Institute of Technology. Department of Biological Engineering
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|a Massachusetts Institute of Technology. Department of Biology
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|a Koch Institute for Integrative Cancer Research at MIT
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|a Oudin, Madeleine Julie
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|a Jonas, Oliver H.
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|a Kosciuk, Tatsiana
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|a Broye, Liliane C.
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|a Candido Guido, Bruna
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|a Wyckoff, Jeffrey
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|a Riquelme, Daisy
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|a Lamar, John Michael
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|a Whittaker, Charles A.
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|a Ma, Duanduan
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|a Langer, Robert
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|a Cima, Michael J.
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|a Hynes, Richard O.
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|a Lauffenburger, Douglas A.
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|a Gertler, Frank
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|a Jonas, Oliver H.
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|a Kosciuk, Tatsiana
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|a Broye, Liliane C.
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|a Candido Guido, Bruna
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|a Wyckoff, Jeffrey
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|a Asokan, Sreeja B.
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|a Whittaker, Charles A.
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|a Ma, Duanduan
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|a Cima, Michael J.
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|a Wisinski, Kari B.
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|a Keely, Patricia J.
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|a Bear, James E.
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|a Gertler, Frank
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|a Riquelme, Daisy Noelia
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|a Lamar, John
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|a Langer, Robert S
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|a Hynes, Richard O
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|a Lauffenburger, Douglas A
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|a Tumor cell-driven extracellular matrix remodeling enables haptotaxis during metastatic progression
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|b American Association for Cancer Research,
|c 2016-03-22T20:22:15Z.
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|z Get fulltext
|u http://hdl.handle.net/1721.1/101752
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|a Fibronectin (FN) is a major component of the tumor microenvironment, but its role in promoting metastasis is incompletely understood. Here we show that FN gradients elicit directional movement of breast cancer cells, in vitro and in vivo. Haptotaxis on FN gradients requires direct interaction between α5β1 integrin and Mena, an actin regulator, and involves increases in focal complex signaling and tumor-cell-mediated extracellular matrix (ECM) remodeling. Compared to Mena, higher levels of the pro-metastatic MenaINV isoform associate with α5, which enables 3D haptotaxis of tumor cells towards the high FN concentrations typically present in perivascular space and in the periphery of breast tumor tissue. MenaINV and FN levels were correlated in two breast cancer cohorts, and high levels of MenaINV were significantly associated with increased tumor recurrence as well as decreased patient survival. Our results identify a novel tumor-cell-intrinsic mechanism that promotes metastasis through ECM remodeling and ECM guided directional migration.
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|a Ludwig Center for Molecular Oncology
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|a Breast Cancer Research Program (U.S.) (post-doctoral fellowship, W81-XWH-12-1-0031)
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|a National Institutes of Health (U.S.) (NIH grant U54-CA112967)
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|a National Institutes of Health (U.S.) (NIH grant R01 CA142833)
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|a Howard Hughes Medical Institute
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|a National Institutes of Health (U.S.) (NIH grant U01 CA143069)
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|a Kathy and Curt Marble Cancer Research Fund (Koch Institute Frontier Award)
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|a Prostate Cancer Foundation
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|a David H. Koch Institute for Integrative Cancer Research at MIT (NCI core grant P30-CA14051)
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|a en_US
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|a Article
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|t Cancer Discovery
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