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


ABSTRACT: 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.

SUBMITTER: Woods EC 

PROVIDER: S-EPMC5739539 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

Woods Elliot C EC   Kai FuiBoon F   Barnes J Matthew JM   Pedram Kayvon K   Pickup Michael W MW   Hollander Michael J MJ   Weaver Valerie M VM   Bertozzi Carolyn R CR  

eLife 20171221


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 displa  ...[more]

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