A bulky glycocalyx fosters metastasis formation by promoting G1 cell cycle progression

• Published in: eLife Vol. 6
• Main Authors: Woods, Elliot C, Kai, FuiBoon, Barnes, J Matthew, Pedram, Kayvon, Pickup, Michael W, Hollander, Michael J, Weaver, Valerie M, Bertozzi, Carolyn R
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 21.12.2017; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: AKT protein; Antigens; Binding sites; Bioengineering; Cancer; Cancer Biology; Carcinogenesis; Cell cycle; Cell growth; cell proliferation; Cell survival; Coatings; Diseases; Displays (Marketing); Ethanol; glycocalyx; Glycoproteins; Growth factors; Immunoglobulins; Integrins; Lungs; Medical prognosis; Metastases; Metastasis; Microscopy; Mucin; Mucins; Physical properties; Polymerization; Proteins; Structural Biology and Molecular Biophysics; Tumor cells; Tumorigenesis; Tumors; glycocalyx; mouse; integrins; cell proliferation; metastasis; cancer biology; structural biology; mucins; biophysics
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.25752

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.