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The cancer glycocalyx mechanically primes integrin-mediated growth and survival

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  • 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
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    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. Tianchi Chen & Cecilia H. Fernández-Espartero & Abigail Illand & Ching-Ting Tsai & Yang Yang & Benjamin Klapholz & Pierre Jouchet & Mélanie Fabre & Olivier Rossier & Bianxiao Cui & Sandrine Lévêque-Fo, 2024. "Actin-driven nanotopography promotes stable integrin adhesion formation in developing tissue," Nature Communications, Nature, vol. 15(1), pages 1-16, 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.
    7. 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.

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