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
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Cited by:
- Stacy A. Malaker & Nicholas M. Riley & D. Judy Shon & Kayvon Pedram & Venkatesh Krishnan & Oliver Dorigo & Carolyn R. Bertozzi, 2022.
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"Reformation of the chondroitin sulfate glycocalyx enables progression of AR-independent prostate cancer,"
Nature Communications, Nature, vol. 13(1), pages 1-14, December.
- 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.
- 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.
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