IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v511y2014i7509d10.1038_nature13535.html
   My bibliography  Save this article

The cancer glycocalyx mechanically primes integrin-mediated growth and survival

Author

Listed:
  • Matthew J. Paszek

    (University of California
    Bay Area Physical Sciences-Oncology Program, University of California
    School of Chemical and Biomolecular Engineering, Cornell University
    Laboratory for Atomic and Solid State Physics and Kavli Institute at Cornell for Nanoscale Science, Cornell University)

  • Christopher C. DuFort

    (University of California
    Bay Area Physical Sciences-Oncology Program, University of California)

  • Olivier Rossier

    (Interdisciplinary Institute for Neuroscience, University of Bordeaux, UMR 5297, F-33000 Bordeaux, France
    CNRS, Interdisciplinary Institute for Neuroscience, University of Bordeaux, UMR 5297, F-33000 Bordeaux, France)

  • Russell Bainer

    (University of California
    Bay Area Physical Sciences-Oncology Program, University of California)

  • Janna K. Mouw

    (University of California)

  • Kamil Godula

    (University of California
    The Molecular Foundry, Lawrence Berkeley National Laboratory
    Present address: Department of Chemistry and Biochemistry, University of California, San Diego, California 92093, USA.)

  • Jason E. Hudak

    (University of California)

  • Jonathon N. Lakins

    (University of California)

  • Amanda C. Wijekoon

    (University of California
    Bay Area Physical Sciences-Oncology Program, University of California)

  • Luke Cassereau

    (University of California
    Bay Area Physical Sciences-Oncology Program, University of California)

  • Matthew G. Rubashkin

    (University of California
    Bay Area Physical Sciences-Oncology Program, University of California)

  • Mark J. Magbanua

    (Helen Diller Family Comprehensive Cancer Center, University of California
    University of California)

  • Kurt S. Thorn

    (University of California)

  • Michael W. Davidson

    (The Florida State University)

  • Hope S. Rugo

    (Helen Diller Family Comprehensive Cancer Center, University of California
    University of California)

  • John W. Park

    (Helen Diller Family Comprehensive Cancer Center, University of California
    University of California)

  • Daniel A. Hammer

    (University of Pennsylvania)

  • Grégory Giannone

    (Interdisciplinary Institute for Neuroscience, University of Bordeaux, UMR 5297, F-33000 Bordeaux, France
    CNRS, Interdisciplinary Institute for Neuroscience, University of Bordeaux, UMR 5297, F-33000 Bordeaux, France)

  • Carolyn R. Bertozzi

    (University of California
    University of California
    Howard Hughes Medical Institute, University of California)

  • Valerie M. Weaver

    (University of California
    Bay Area Physical Sciences-Oncology Program, University of California
    Helen Diller Family Comprehensive Cancer Center, University of California
    University of California)

Abstract

Malignancy is associated with altered expression of glycans and glycoproteins that contribute to the cellular glycocalyx. We constructed a glycoprotein expression signature, which revealed that metastatic tumours upregulate expression of bulky glycoproteins. A computational model predicted that these glycoproteins would influence transmembrane receptor spatial organization and function. We tested this prediction by investigating whether bulky glycoproteins in the glycocalyx promote a tumour phenotype in human cells by increasing integrin adhesion and signalling. Our data revealed that a bulky glycocalyx facilitates integrin clustering by funnelling active integrins into adhesions and altering integrin state by applying tension to matrix-bound integrins, independent of actomyosin contractility. Expression of large tumour-associated glycoproteins in non-transformed mammary cells promoted focal adhesion assembly and facilitated integrin-dependent growth factor signalling to support cell growth and survival. Clinical studies revealed that large glycoproteins are abundantly expressed on circulating tumour cells from patients with advanced disease. Thus, a bulky glycocalyx is a feature of tumour cells that could foster metastasis by mechanically enhancing cell-surface receptor function.

Suggested Citation

  • Matthew J. Paszek & Christopher C. DuFort & Olivier Rossier & Russell Bainer & Janna K. Mouw & Kamil Godula & Jason E. Hudak & Jonathon N. Lakins & Amanda C. Wijekoon & Luke Cassereau & Matthew G. Rub, 2014. "The cancer glycocalyx mechanically primes integrin-mediated growth and survival," Nature, Nature, vol. 511(7509), pages 319-325, July.
  • Handle: RePEc:nat:nature:v:511:y:2014:i:7509:d:10.1038_nature13535
    DOI: 10.1038/nature13535
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature13535
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/nature13535?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Stacy A. Malaker & Nicholas M. Riley & D. Judy Shon & Kayvon Pedram & Venkatesh Krishnan & Oliver Dorigo & Carolyn R. Bertozzi, 2022. "Revealing the human mucinome," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Matthew R. Pawlak & Adam T. Smiley & Maria Paz Ramirez & Marcus D. Kelly & Ghaidan A. Shamsan & Sarah M. Anderson & Branden A. Smeester & David A. Largaespada & David J. Odde & Wendy R. Gordon, 2023. "RAD-TGTs: high-throughput measurement of cellular mechanotype via rupture and delivery of DNA tension probes," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    3. Serena Petracchini & Daniel Hamaoui & Anne Doye & Atef Asnacios & Florian Fage & Elisa Vitiello & Martial Balland & Sebastien Janel & Frank Lafont & Mukund Gupta & Benoit Ladoux & Jerôme Gilleron & Te, 2022. "Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    4. Nader Al-Nakouzi & Chris Kedong Wang & Htoo Zarni Oo & Irina Nelepcu & Nada Lallous & Charlotte B. Spliid & Nastaran Khazamipour & Joey Lo & Sarah Truong & Colin Collins & Desmond Hui & Shaghayegh Esf, 2022. "Reformation of the chondroitin sulfate glycocalyx enables progression of AR-independent prostate cancer," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Chih-Hao Lu & Kayvon Pedram & Ching-Ting Tsai & Taylor Jones & Xiao Li & Melissa L. Nakamoto & Carolyn R. Bertozzi & Bianxiao Cui, 2022. "Membrane curvature regulates the spatial distribution of bulky glycoproteins," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. Yihong Zhong & Lijia Xu & Chen Yang & Le Xu & Guyu Wang & Yuna Guo & Songtao Cheng & Xiao Tian & Changjiang Wang & Ran Xie & Xiaojian Wang & Lin Ding & Huangxian Ju, 2023. "Site-selected in situ polymerization for living cell surface engineering," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:511:y:2014:i:7509:d:10.1038_nature13535. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.