@article {65256,
	title = {Trans-endocytosis of intact IL-15Rα-IL-15 complex from presenting cells into NK cells favors signaling for proliferation.},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {117},
	year = {2020},
	month = {2020 Jan 07},
	pages = {522-531},
	abstract = {<p>Interleukin 15 (IL-15) is an essential cytokine for the survival and proliferation of natural killer (NK) cells. IL-15 activates signaling by the β and common γ (γ) chain heterodimer of the IL-2 receptor through -presentation by cells expressing IL-15 bound to the α chain of the IL-15 receptor (IL-15Rα). We show here that membrane-associated IL-15Rα-IL-15 complexes are transferred from presenting cells to NK cells through -endocytosis and contribute to the phosphorylation of ribosomal protein S6 and NK cell proliferation. NK cell interaction with soluble or surface-bound IL-15Rα-IL-15 complex resulted in Stat5 phosphorylation and NK cell survival at a concentration or density of the complex much lower than required to stimulate S6 phosphorylation. Despite this efficient response, Stat5 phosphorylation was reduced after inhibition of metalloprotease-induced IL-15Rα-IL-15 shedding from -presenting cells, whereas S6 phosphorylation was unaffected. Conversely, inhibition of -endocytosis by silencing of the small GTPase TC21 or expression of a dominant-negative TC21 reduced S6 phosphorylation but not Stat5 phosphorylation. Thus, -endocytosis of membrane-associated IL-15Rα-IL-15 provides a mode of regulating NK cells that is not afforded to IL-2 and is distinct from activation by soluble IL-15. These results may explain the strict IL-15 dependence of NK cells and illustrate how the cellular compartment in which receptor-ligand interaction occurs can influence functional outcome.</p>
},
	issn = {1091-6490},
	doi = {10.1073/pnas.1911678117},
	author = {Anton, Olga M and Peterson, Mary E and Hollander, Michael J and Dorward, David W and Arora, Gunjan and Traba, Javier and Rajagopalan, Sumati and Snapp, Erik L and Garcia, K Christopher and Waldmann, Thomas A and Long, Eric O}
}
@article {65894,
	title = {A bulky glycocalyx fosters metastasis formation by promoting G1 cell cycle progression},
	journal = {eLife},
	volume = {6},
	year = {2017},
	month = {Sep-12-2018},
	abstract = {<p>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.</p>
},
	doi = {https://doi.org/10.7554/eLife.25752},
	url = {https://elifesciences.org/articles/25752},
	author = {Woods, Elliot C and Kai, FuiBoon and Barnes, J Matthew and Pedram, Kayvon and Pickup, Michael W and Hollander, Michael J and Weaver, Valerie M and Bertozzi, Carolyn R}
}
