A bulky glycocalyx fosters metastasis formation by promoting G1 cell cycle progression
| Autor: | J. Matthew Barnes, FuiBoon Kai, Valerie M. Weaver, Michael J. Hollander, Elliot C. Woods, Carolyn R. Bertozzi, Kayvon Pedram, Michael W. Pickup |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Mouse Carcinogenesis Structural Biology and Molecular Biophysics medicine.disease_cause Metastasis Mice 0302 clinical medicine biophysics 2.1 Biological and endogenous factors structural biology Aetiology Biology (General) MUC1 Cancer cancer biology Cancer Biology 0303 health sciences Tumor Chemistry General Neuroscience Cell Cycle General Medicine Cell cycle Ectodomain 030220 oncology & carcinogenesis Medicine Stem Cell Research - Nonembryonic - Non-Human Research Article QH301-705.5 Science Integrin Mammary Neoplasms Animal Biology Glycocalyx General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences Rare Diseases Cell Line Tumor medicine Animals Humans metastasis mouse 030304 developmental biology General Immunology and Microbiology Animal Cell growth Mammary Neoplasms Mucin-1 Mucin mucins Stem Cell Research medicine.disease Disease Models Animal cell proliferation 030104 developmental biology Disease Models Immunology Cancer cell biology.protein integrins Cancer research Biochemistry and Cell Biology glycocalyx |
| Zdroj: | eLife, Vol 6 (2017) eLife |
| ISSN: | 2050-084X |
| DOI: | 10.7554/elife.25752 |
| Popis: | Metastasis depends upon cancer cell growth and survival within the metastatic niche. Tumors which remodel their glycocalyces, by overexpressing bulky glycoproteins like mucins, exhibit a higher predisposition to metastasize, but the role of mucins in oncogenesis remains poorly understood. Here we report that a bulky glycocalyx promotes the expansion of disseminated tumor cells in vivo by fostering integrin adhesion assembly to permit G1 cell cycle progression. We engineered tumor cells to display glycocalyces of various thicknesses by coating them with synthetic mucin-mimetic glycopolymers. Cells adorned with longer glycopolymers showed increased metastatic potential, enhanced cell cycle progression, and greater levels of integrin-FAK mechanosignaling and Akt signaling in a syngeneic mouse model of metastasis. These effects were mirrored by expression of the ectodomain of cancer-associated mucin MUC1. These findings functionally link mucinous proteins with tumor aggression, and offer a new view of the cancer glycocalyx as a major driver of disease progression. |
| Databáze: | OpenAIRE |
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